rs1240656822

Variant names:

• chr8-144516315-G-A
• rs1240656822
• ENST00000621189.4:c.-268C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144516315-G-A
• chr8-144516315-G-C

Variant summary

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

The ENST00000621189.4(RECQL4):​c.-268C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RECQL4 ENST00000621189.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.01
• 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=-0.88).
• BP6: Variant 8-144516315-G-A is Benign according to our data. Variant chr8-144516315-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 529102.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621189.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.804C>T	p.Pro268Pro	synonymous	Exon 5 of 21	NP_004251.4
	RECQL4	NM_001413023.1		c.-268C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 19	NP_001399952.1
	RECQL4	NM_001413041.1		c.-330C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 19	NP_001399970.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000621189.4	TSL:1	c.-268C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 20	ENSP00000483145.1
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.804C>T	p.Pro268Pro	synonymous	Exon 5 of 21	ENSP00000482313.2
	RECQL4	ENST00000621189.4	TSL:1	c.-268C>T		5_prime_UTR	Exon 4 of 20	ENSP00000483145.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 242728 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457610 Hom.: 0 Cov.: 66 AF XY: 0.00000138 AC XY: 1 AN XY: 724916

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 86016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111096

Other (OTH) AF: 0.00 AC: 0 AN: 60290

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

Dec 27, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.65
PhyloP100		-6.0
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1

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: rs1240656822; hg19: chr8-145741699;