dbSNP rs820200: RECQL5:c.1230-4282G>T (chr17-75635950-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004259.7(RECQL5):c.1230-4282G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 736,904 control chromosomes in the GnomAD database, including 43,093 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8158 hom., cov: 33)

Exomes 𝑓: 0.34 ( 34935 hom. )

Consequence

RECQL5
NM_004259.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.221

Publications

9 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 links:

SMIM5 (HGNC:40030): (small integral membrane protein 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 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.1230-4282G>T		intron	N/A	NP_004250.4
	SMIM5	NM_001162995.3	MANE Select	c.-37+1748C>A		intron	N/A	NP_001156467.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RECQL5	ENST00000317905.10	TSL:1 MANE Select	c.1230-4282G>T	intron	N/A	ENSP00000317636.5
SMIM5	ENST00000375215.3	TSL:1 MANE Select	c.-37+1748C>A	intron	N/A	ENSP00000364363.3
RECQL5	ENST00000423245.6	TSL:1	c.1149-4282G>T	intron	N/A	ENSP00000394820.2

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48685

AN:

152066

Hom.:

8159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.327

GnomAD4 exome

AF:

0.344

AC:

201394

AN:

584720

Hom.:

34935

AF XY:

0.345

AC XY:

94396

AN XY:

273506

show subpopulations

African (AFR)

AF:

0.237

AC:

2541

AN:

10740

American (AMR)

AF:

0.394

AC:

270

AN:

686

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1637

AN:

3662

East Asian (EAS)

AF:

0.486

AC:

1201

AN:

2470

South Asian (SAS)

AF:

0.401

AC:

4615

AN:

11512

European-Finnish (FIN)

AF:

0.360

AC:

AN:

200

Middle Eastern (MID)

AF:

0.384

AC:

444

AN:

1156

European-Non Finnish (NFE)

AF:

0.343

AC:

183792

AN:

535072

Other (OTH)

AF:

0.355

AC:

6822

AN:

19222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

6218

12436

18655

24873

31091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8162

16324

24486

32648

40810

<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:

0.320

AC:

48702

AN:

152184

Hom.:

8158

Cov.:

AF XY:

0.323

AC XY:

24054

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.230

AC:

9554

AN:

41546

American (AMR)

AF:

0.373

AC:

5706

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1449

AN:

3470

East Asian (EAS)

AF:

0.487

AC:

2522

AN:

5176

South Asian (SAS)

AF:

0.393

AC:

1897

AN:

4830

European-Finnish (FIN)

AF:

0.340

AC:

3594

AN:

10570

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

22993

AN:

67978

Other (OTH)

AF:

0.323

AC:

683

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1703

3406

5108

6811

8514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.339

Hom.:

2977

Bravo

AF:

0.323

Asia WGS

AF:

0.396

AC:

1378

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.3

(source)

DANN

Benign

0.74

PhyloP100

0.22

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