Genetic Variant NM_014424.5:c.99T>C (chr1-16017865-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.99T>C(p.Ala33Ala) 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 1,613,290 control chromosomes in the GnomAD database, including 284,480 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 ( 28840 hom., cov: 35)

Exomes 𝑓: 0.59 ( 255640 hom. )

Consequence

HSPB7
NM_014424.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

29 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:

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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=-0.63).

BP7

Synonymous conserved (PhyloP=1.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPB7	NM_014424.5 link	c.99T>C	p.Ala33Ala	synonymous_variant	Exon 1 of 3	ENST00000311890.14	NP_055239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPB7	ENST00000311890.14 link	c.99T>C	p.Ala33Ala	synonymous_variant	Exon 1 of 3	1	NM_014424.5	ENSP00000310111.9

Frequencies

GnomAD3 genomes

AF:

0.611

AC:

92890

AN:

152084

Hom.:

28818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.593

Gnomad OTH

AF:

0.623

GnomAD2 exomes

AF:

0.576

AC:

142092

AN:

246776

AF XY:

0.581

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.511

Gnomad EAS exome

AF:

0.752

Gnomad FIN exome

AF:

0.566

Gnomad NFE exome

AF:

0.592

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.590

AC:

861322

AN:

1461088

Hom.:

255640

Cov.:

AF XY:

0.590

AC XY:

428741

AN XY:

726814

show subpopulations

African (AFR)

AF:

0.701

AC:

23446

AN:

33468

American (AMR)

AF:

0.403

AC:

17975

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

13454

AN:

26128

East Asian (EAS)

AF:

0.728

AC:

28901

AN:

39684

South Asian (SAS)

AF:

0.586

AC:

50506

AN:

86198

European-Finnish (FIN)

AF:

0.565

AC:

30119

AN:

53328

Middle Eastern (MID)

AF:

0.610

AC:

3515

AN:

5760

European-Non Finnish (NFE)

AF:

0.591

AC:

656992

AN:

1111534

Other (OTH)

AF:

0.603

AC:

36414

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

19847

39695

59542

79390

99237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18036

36072

54108

72144

90180

<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:

0.611

AC:

92952

AN:

152202

Hom.:

28840

Cov.:

AF XY:

0.605

AC XY:

45010

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.690

AC:

28660

AN:

41554

American (AMR)

AF:

0.489

AC:

7478

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1771

AN:

3472

East Asian (EAS)

AF:

0.775

AC:

4007

AN:

5168

South Asian (SAS)

AF:

0.597

AC:

2881

AN:

4824

European-Finnish (FIN)

AF:

0.556

AC:

5895

AN:

10600

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.593

AC:

40285

AN:

67966

Other (OTH)

AF:

0.621

AC:

1314

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

1983

3967

5950

7934

9917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.600

Hom.:

12059

Bravo

AF:

0.606

Asia WGS

AF:

0.636

AC:

2211

AN:

3478

EpiCase

AF:

0.589

EpiControl

AF:

0.593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.5

PromoterAI

-0.038

Neutral

(source)

Mutation Taster

=79/21

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