dbSNP rs945417: HSPB7:c.337-278G>C (chr1-16018130-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001349682.2(HSPB7):c.337-278G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,546,386 control chromosomes in the GnomAD database, including 251,782 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 0.60 ( 28043 hom., cov: 33)

Exomes 𝑓: 0.56 ( 223739 hom. )

Consequence

HSPB7
NM_001349682.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.795

Publications

15 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.017).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPB7	NM_014424.5 link	c.-167G>C		upstream_gene_variant		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.-167G>C		upstream_gene_variant		1	NM_014424.5	ENSP00000310111.9		Q9UBY9-1

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

91041

AN:

151978

Hom.:

28017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.719

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.608

GnomAD2 exomes

AF:

0.546

AC:

82419

AN:

151064

AF XY:

0.551

show subpopulations

Gnomad AFR exome

AF:

0.722

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.758

Gnomad FIN exome

AF:

0.524

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.564

AC:

786154

AN:

1394290

Hom.:

223739

Cov.:

AF XY:

0.564

AC XY:

387679

AN XY:

687786

show subpopulations

African (AFR)

AF:

0.731

AC:

23029

AN:

31500

American (AMR)

AF:

0.405

AC:

14394

AN:

35582

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

11432

AN:

25050

East Asian (EAS)

AF:

0.730

AC:

25943

AN:

35540

South Asian (SAS)

AF:

0.558

AC:

43793

AN:

78504

European-Finnish (FIN)

AF:

0.528

AC:

25277

AN:

47910

Middle Eastern (MID)

AF:

0.560

AC:

3108

AN:

5550

European-Non Finnish (NFE)

AF:

0.562

AC:

605739

AN:

1076950

Other (OTH)

AF:

0.579

AC:

33439

AN:

57704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

18901

37802

56704

75605

94506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17258

34516

51774

69032

86290

<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:

0.599

AC:

91107

AN:

152096

Hom.:

28043

Cov.:

AF XY:

0.592

AC XY:

44046

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.719

AC:

29840

AN:

41494

American (AMR)

AF:

0.476

AC:

7274

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1556

AN:

3472

East Asian (EAS)

AF:

0.774

AC:

3994

AN:

5160

South Asian (SAS)

AF:

0.577

AC:

2782

AN:

4822

European-Finnish (FIN)

AF:

0.519

AC:

5498

AN:

10590

Middle Eastern (MID)

AF:

0.640

AC:

187

AN:

292

European-Non Finnish (NFE)

AF:

0.564

AC:

38344

AN:

67952

Other (OTH)

AF:

0.606

AC:

1280

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1903

3806

5708

7611

9514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.562

Hom.:

7863

Bravo

AF:

0.598

Asia WGS

AF:

0.631

AC:

2195

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.80

PromoterAI

-0.037

Neutral

(source)

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over