rs1172497739

chr8-144513144-G-Achr8-144513144-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004260.4(RECQL4):c.2464-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,449,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: RECQL4 NM_004260.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00008355
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.723

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-144513144-G-A is Benign according to our data. Variant chr8-144513144-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774011.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144513144-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4	c.2464-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6	c.2464-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004260.4	P1
RECQL4	ENST00000621189.4	c.1393-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
	ENST00000580385.1	n.271+307G>A		intron_variant, non_coding_transcript_variant		3
RECQL4	ENST00000534626.6	c.635-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 146534 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000302

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 26 AN: 1303238 Hom.: 0 Cov.: 67 AF XY: 0.0000296 AC XY: 19 AN XY: 640814

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.0000285

Gnomad4 NFE exome AF: 0.0000226

Gnomad4 OTH exome AF: 0.0000195

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 146534 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 71256

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000302

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Baller-Gerold syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.61
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000084
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs1172497739; hg19: chr8-145738527;