Variant 12-21475857-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002907.4(RECQL):c.950-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,544,720 control chromosomes in the GnomAD database, including 177,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18451 hom., cov: 33)

Exomes 𝑓: 0.48 ( 158575 hom. )

Consequence

RECQL
NM_002907.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.982

Variant links:

Genes affected

RECQL (HGNC:9948): (RecQ like helicase) The protein encoded by this gene is a member of the RecQ DNA helicase family. DNA helicases are enzymes involved in various types of DNA repair, including mismatch repair, nucleotide excision repair and direct repair. The encoded protein is involved in the processing of Holliday junctions, the suppression of sister chromatid exchanges, telomere maintenance, and is required for genotoxic stress resistance. Defects in this gene have been associated with several types of cancer. [provided by RefSeq, Jan 2017]

RECQL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 12-21475857-T-C is Benign according to our data. Variant chr12-21475857-T-C is described in ClinVar as [Benign]. Clinvar id is 679686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL	NM_002907.4 linkuse as main transcript	c.950-33A>G		intron_variant		ENST00000444129.7	NP_002898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL	ENST00000444129.7 linkuse as main transcript	c.950-33A>G		intron_variant		2	NM_002907.4	ENSP00000416739.2		P46063
RECQL	ENST00000421138.6 linkuse as main transcript	c.950-33A>G		intron_variant		1		ENSP00000395449.2		P46063

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74602

AN:

151742

Hom.:

18424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.544

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.491

GnomAD3 exomes

AF:

0.480

AC:

115804

AN:

241328

Hom.:

27741

AF XY:

0.477

AC XY:

62485

AN XY:

131088

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.460

Gnomad ASJ exome

AF:

0.429

Gnomad EAS exome

AF:

0.566

Gnomad SAS exome

AF:

0.440

Gnomad FIN exome

AF:

0.509

Gnomad NFE exome

AF:

0.479

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

AF:

0.476

AC:

662925

AN:

1392860

Hom.:

158575

Cov.:

AF XY:

0.475

AC XY:

330385

AN XY:

696156

show subpopulations

Gnomad4 AFR exome

AF:

0.505

Gnomad4 AMR exome

AF:

0.467

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.564

Gnomad4 SAS exome

AF:

0.437

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.474

Gnomad4 OTH exome

AF:

0.487

GnomAD4 genome

AF:

0.492

AC:

74672

AN:

151860

Hom.:

18451

Cov.:

AF XY:

0.491

AC XY:

36474

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.508

Gnomad4 AMR

AF:

0.493

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.544

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.498

Gnomad4 NFE

AF:

0.483

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.481

Hom.:

17456

Bravo

AF:

0.493

Asia WGS

AF:

0.546

AC:

1900

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.5

DANN

Benign

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over