dbSNP rs2159943: RECQL:c.1355+30T>C (chr12-21474811-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002907.4(RECQL):c.1355+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,598,170 control chromosomes in the GnomAD database, including 155,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 11036 hom., cov: 33)

Exomes 𝑓: 0.44 ( 144356 hom. )

Consequence

RECQL
NM_002907.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.116

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

RECON progeroid syndrome
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
familial ovarian cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

RECQL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-21474811-A-G is Benign according to our data. Variant chr12-21474811-A-G is described in ClinVar as Benign. ClinVar VariationId is 679689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002907.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL	NM_002907.4	MANE Select	c.1355+30T>C		intron	N/A	NP_002898.2
	RECQL	NM_032941.3		c.1355+30T>C		intron	N/A	NP_116559.1	P46063

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RECQL	ENST00000444129.7	TSL:2 MANE Select	c.1355+30T>C	intron	N/A	ENSP00000416739.2	P46063
RECQL	ENST00000421138.6	TSL:1	c.1355+30T>C	intron	N/A	ENSP00000395449.2	P46063
RECQL	ENST00000965023.1		c.1385+30T>C	intron	N/A	ENSP00000635082.1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53775

AN:

151844

Hom.:

11039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.515

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.438

Gnomad OTH

AF:

0.347

GnomAD2 exomes

AF:

0.435

AC:

107742

AN:

247490

AF XY:

0.442

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.483

Gnomad ASJ exome

AF:

0.457

Gnomad EAS exome

AF:

0.432

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.440

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.442

AC:

639569

AN:

1446210

Hom.:

144356

Cov.:

AF XY:

0.445

AC XY:

320331

AN XY:

720002

show subpopulations

African (AFR)

AF:

0.109

AC:

3600

AN:

33026

American (AMR)

AF:

0.471

AC:

20687

AN:

43882

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

11838

AN:

25816

East Asian (EAS)

AF:

0.434

AC:

17165

AN:

39550

South Asian (SAS)

AF:

0.513

AC:

43845

AN:

85522

European-Finnish (FIN)

AF:

0.461

AC:

24535

AN:

53202

Middle Eastern (MID)

AF:

0.307

AC:

1751

AN:

5700

European-Non Finnish (NFE)

AF:

0.447

AC:

491359

AN:

1099760

Other (OTH)

AF:

0.415

AC:

24789

AN:

59752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

16561

33122

49683

66244

82805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14844

29688

44532

59376

74220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.354

AC:

53771

AN:

151960

Hom.:

11036

Cov.:

AF XY:

0.360

AC XY:

26721

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.127

AC:

5266

AN:

41532

American (AMR)

AF:

0.413

AC:

6298

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

1615

AN:

3462

East Asian (EAS)

AF:

0.451

AC:

2336

AN:

5176

South Asian (SAS)

AF:

0.516

AC:

2488

AN:

4820

European-Finnish (FIN)

AF:

0.465

AC:

4914

AN:

10570

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.438

AC:

29712

AN:

67826

Other (OTH)

AF:

0.342

AC:

722

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1679

3358

5038

6717

8396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.399

Hom.:

2925

Bravo

AF:

0.338

Asia WGS

AF:

0.404

AC:

1403

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

(source)

DANN

Benign

0.68

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over