chr17-75631459-T-C

Variant names:

Variant summary

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

The NM_004259.7(RECQL5):c.1439A>G(p.Asp480Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,606,496 control chromosomes in the GnomAD database, including 46,957 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3916 hom., cov: 35)

Exomes 𝑓: 0.24 ( 43041 hom. )

Consequence

RECQL5
NM_004259.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.40

Publications

46 publications found

Variant links:

Genes affected

RECQL5 (HGNC:9950): (RecQ like helicase 5) The protein encoded by this gene is a helicase that is important for genome stability. The encoded protein also prevents aberrant homologous recombination by displacing RAD51 from ssDNA. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

RECQL5 Gene-Disease associations (from GenCC):

breast cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
coronary artery disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RECQL5 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 (MetaRNN=0.0047875345).

BP6

Variant 17-75631459-T-C is Benign according to our data. Variant chr17-75631459-T-C is described in ClinVar as Benign. ClinVar VariationId is 1261428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004259.7. 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
	RECQL5	NM_004259.7	MANE Select	c.1439A>G	p.Asp480Gly	missense	Exon 9 of 20	NP_004250.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RECQL5	ENST00000317905.10	TSL:1 MANE Select	c.1439A>G	p.Asp480Gly	missense	Exon 9 of 20	ENSP00000317636.5
RECQL5	ENST00000423245.6	TSL:1	c.1358A>G	p.Asp453Gly	missense	Exon 9 of 20	ENSP00000394820.2
RECQL5	ENST00000443199.6	TSL:1	n.975A>G		non_coding_transcript_exon	Exon 2 of 13

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33903

AN:

152130

Hom.:

3918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.220

GnomAD2 exomes

AF:

0.257

AC:

63609

AN:

247260

AF XY:

0.259

show subpopulations

Gnomad AFR exome

AF:

0.181

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.239

AC:

347876

AN:

1454248

Hom.:

43041

Cov.:

AF XY:

0.242

AC XY:

174596

AN XY:

721874

show subpopulations

African (AFR)

AF:

0.187

AC:

6235

AN:

33338

American (AMR)

AF:

0.337

AC:

15016

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

6265

AN:

26072

East Asian (EAS)

AF:

0.330

AC:

13014

AN:

39466

South Asian (SAS)

AF:

0.338

AC:

29103

AN:

86150

European-Finnish (FIN)

AF:

0.209

AC:

10951

AN:

52434

Middle Eastern (MID)

AF:

0.249

AC:

1429

AN:

5746

European-Non Finnish (NFE)

AF:

0.227

AC:

251641

AN:

1106454

Other (OTH)

AF:

0.237

AC:

14222

AN:

59986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

14383

28765

43148

57530

71913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8928

17856

26784

35712

44640

<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:

0.223

AC:

33906

AN:

152248

Hom.:

3916

Cov.:

AF XY:

0.226

AC XY:

16816

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.187

AC:

7755

AN:

41566

American (AMR)

AF:

0.279

AC:

4271

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

774

AN:

3470

East Asian (EAS)

AF:

0.282

AC:

1455

AN:

5166

South Asian (SAS)

AF:

0.329

AC:

1589

AN:

4828

European-Finnish (FIN)

AF:

0.204

AC:

2168

AN:

10610

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15253

AN:

67984

Other (OTH)

AF:

0.216

AC:

457

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1445

2890

4335

5780

7225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.229

Hom.:

10844

Bravo

AF:

0.229

TwinsUK

AF:

0.224

AC:

830

ALSPAC

AF:

0.229

AC:

883

ESP6500AA

AF:

0.166

AC:

677

ESP6500EA

AF:

0.218

AC:

1829

ExAC

AF:

0.251

AC:

30390

Asia WGS

AF:

0.288

AC:

999

AN:

3478

EpiCase

AF:

0.234

EpiControl

AF:

0.226

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 25, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24213927)

RECQL5-related disorder

Benign:1

Nov 04, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.97

PhyloP100

2.4

PrimateAI

Benign

0.47

PROVEAN

Benign

0.39

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

0.87

Polyphen

0.0

Vest4

0.12

MPC

0.15

ClinPred

0.011

GERP RS

6.0

Varity_R

0.057

gMVP

0.47

Mutation Taster

=98/2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over