rs34271972

chr8-144513458-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_004260.4(RECQL4):c.2223C>T(p.Ala741=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,609,842 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A741A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.17

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 Benign. Variant got -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-144513458-G-A is Benign according to our data. Variant chr8-144513458-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 239718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144513458-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-6.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00185 (282/152348) while in subpopulation AFR AF= 0.00647 (269/41574). AF 95% confidence interval is 0.00584. There are 1 homozygotes in gnomad4. There are 139 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4	c.2223C>T	p.Ala741=	synonymous_variant	14/21	ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6	c.2223C>T	p.Ala741=	synonymous_variant	14/21	1	NM_004260.4	P1
RECQL4	ENST00000621189.4	c.1152C>T	p.Ala384=	synonymous_variant	13/20	1
	ENST00000580385.1	n.272-148G>A		intron_variant, non_coding_transcript_variant		3
RECQL4	ENST00000534626.6	c.594C>T	p.Ala198=	synonymous_variant	5/8	5

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 281 AN: 152230 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00647

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000457 AC: 111 AN: 243068 Hom.: 0 AF XY: 0.000353 AC XY: 47 AN XY: 133222

Gnomad AFR exome AF: 0.00634

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000982

Gnomad FIN exome AF: 0.0000519

Gnomad NFE exome AF: 0.0000272

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000209 AC: 304 AN: 1457494 Hom.: 0 Cov.: 48 AF XY: 0.000194 AC XY: 141 AN XY: 725222

Gnomad4 AFR exome AF: 0.00690

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.0000202

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.000365

GnomAD4 genome AF: 0.00185 AC: 282 AN: 152348 Hom.: 1 Cov.: 33 AF XY: 0.00187 AC XY: 139 AN XY: 74502

Gnomad4 AFR AF: 0.00647

Gnomad4 AMR AF: 0.000718

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000919 Hom.: 0

Bravo AF: 0.00226

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 01, 2017

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2021

- -

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, criteria provided, single submitter

curation

Sema4, Sema4

Jan 31, 2021

- -

Baller-Gerold syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.073
Dann	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs34271972; hg19: chr8-145738842; COSMIC: COSV99467216; COSMIC: COSV99467216;