rs373192242

Variant names:

• chr8-144515143-C-G
• rs373192242
• NM_004260.4:c.1483+7G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-144515143-C-G
• chr8-144515143-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004260.4(RECQL4):​c.1483+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: RECQL4 NM_004260.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.48
• Publications: 0 publications found

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

RECQL4 Gene-Disease associations (from GenCC):

• Baller-Gerold syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
• Rothmund-Thomson syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Rothmund-Thomson syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
• osteosarcoma

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• rapadilino syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-144515143-C-G is Benign according to our data. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144515143-C-G is described in CliVar as Likely_benign. Clinvar id is 1638191.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.1483+7G>C		splice_region_variant, intron_variant	Intron 8 of 20	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1483+7G>C		splice_region_variant, intron_variant	Intron 8 of 20	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.412+7G>C		splice_region_variant, intron_variant	Intron 7 of 19	1		ENSP00000483145.1
RECQL4	ENST00000532846.2	c.367+7G>C		splice_region_variant, intron_variant	Intron 4 of 8	5		ENSP00000476551.1
RECQL4	ENST00000688394.1	n.506+7G>C		splice_region_variant, intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Baller-Gerold syndrome Benign:1

Sep 03, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.033
DANN	Benign	0.70
PhyloP100		-2.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373192242; hg19: chr8-145740527;