dbSNP rs1739840: HSPB7:p.Thr117Thr (chr1-16015742-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014424.5(HSPB7):c.351T>C(p.Thr117Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,588,860 control chromosomes in the GnomAD database, including 281,129 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 0.61 ( 29272 hom., cov: 33)

Exomes 𝑓: 0.59 ( 251857 hom. )

Consequence

HSPB7
NM_014424.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.44

Publications

24 publications found

Variant links:

Genes affected

HSPB7 (HGNC:5249): (heat shock protein family B (small) member 7) This gene encodes a small heat shock family B member that can heterodimerize with similar heat shock proteins. Defects in this gene are associated with advanced heart failure. In addition, the encoded protein may be a tumor suppressor in the p53 pathway, with defects in this gene being associated with renal cell carcinoma. [provided by RefSeq, Mar 2017]

HSPB7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP7

Synonymous conserved (PhyloP=-8.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPB7	NM_014424.5 link	c.351T>C	p.Thr117Thr	synonymous_variant	Exon 3 of 3	ENST00000311890.14	NP_055239.1	Q9UBY9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPB7	ENST00000311890.14 link	c.351T>C	p.Thr117Thr	synonymous_variant	Exon 3 of 3	1	NM_014424.5	ENSP00000310111.9		Q9UBY9-1

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93453

AN:

151940

Hom.:

29251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.778

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.625

GnomAD2 exomes

AF:

0.580

AC:

138499

AN:

238962

AF XY:

0.584

show subpopulations

Gnomad AFR exome

AF:

0.702

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.753

Gnomad FIN exome

AF:

0.568

Gnomad NFE exome

AF:

0.594

Gnomad OTH exome

AF:

0.572

GnomAD4 exome

AF:

0.590

AC:

847795

AN:

1436802

Hom.:

251857

Cov.:

AF XY:

0.590

AC XY:

419675

AN XY:

710856

show subpopulations

African (AFR)

AF:

0.715

AC:

23630

AN:

33072

American (AMR)

AF:

0.403

AC:

17642

AN:

43766

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

13014

AN:

25108

East Asian (EAS)

AF:

0.729

AC:

28554

AN:

39176

South Asian (SAS)

AF:

0.587

AC:

49452

AN:

84274

European-Finnish (FIN)

AF:

0.564

AC:

28571

AN:

50620

Middle Eastern (MID)

AF:

0.611

AC:

3400

AN:

5564

European-Non Finnish (NFE)

AF:

0.591

AC:

647702

AN:

1095950

Other (OTH)

AF:

0.605

AC:

35830

AN:

59272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

18687

37375

56062

74750

93437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18022

36044

54066

72088

90110

<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:

0.615

AC:

93514

AN:

152058

Hom.:

29272

Cov.:

AF XY:

0.610

AC XY:

45299

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.704

AC:

29228

AN:

41500

American (AMR)

AF:

0.492

AC:

7525

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1779

AN:

3466

East Asian (EAS)

AF:

0.777

AC:

4000

AN:

5148

South Asian (SAS)

AF:

0.597

AC:

2878

AN:

4820

European-Finnish (FIN)

AF:

0.556

AC:

5875

AN:

10572

Middle Eastern (MID)

AF:

0.668

AC:

195

AN:

292

European-Non Finnish (NFE)

AF:

0.592

AC:

40253

AN:

67944

Other (OTH)

AF:

0.623

AC:

1316

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1886

3773

5659

7546

9432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<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:

0.595

Hom.:

10746

Bravo

AF:

0.611

Asia WGS

AF:

0.638

AC:

2218

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0050

(source)

DANN

Benign

0.63

PhyloP100

-8.4

Mutation Taster

=99/1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over