dbSNP rs1572381: HSPB7:n.45C>T (chr1-16017999-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The ENST00000442459.2(HSPB7):n.45C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,611,614 control chromosomes in the GnomAD database, including 284,164 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 ( 28775 hom., cov: 35)

Exomes 𝑓: 0.59 ( 255389 hom. )

Consequence

HSPB7
ENST00000442459.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.824

Publications

21 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=0.056).

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.-36C>T		5_prime_UTR_variant	Exon 1 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.-36C>T		5_prime_UTR_variant	Exon 1 of 3	1	NM_014424.5	ENSP00000310111.9		Q9UBY9-1

Frequencies

GnomAD3 genomes

AF:

0.610

AC:

92762

AN:

152042

Hom.:

28754

Cov.:

show subpopulations

Gnomad AFR

AF:

0.688

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.511

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:

0.622

GnomAD2 exomes

AF:

0.576

AC:

139812

AN:

242582

AF XY:

0.581

show subpopulations

Gnomad AFR exome

AF:

0.687

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.512

Gnomad EAS exome

AF:

0.753

Gnomad FIN exome

AF:

0.567

Gnomad NFE exome

AF:

0.593

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.590

AC:

860448

AN:

1459454

Hom.:

255389

Cov.:

AF XY:

0.590

AC XY:

428290

AN XY:

725940

show subpopulations

African (AFR)

AF:

0.699

AC:

23387

AN:

33464

American (AMR)

AF:

0.403

AC:

17999

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

13440

AN:

26094

East Asian (EAS)

AF:

0.729

AC:

28901

AN:

39668

South Asian (SAS)

AF:

0.586

AC:

50521

AN:

86194

European-Finnish (FIN)

AF:

0.565

AC:

29509

AN:

52226

Middle Eastern (MID)

AF:

0.610

AC:

3494

AN:

5732

European-Non Finnish (NFE)

AF:

0.591

AC:

656842

AN:

1111186

Other (OTH)

AF:

0.603

AC:

36355

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20588

41176

61763

82351

102939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.610

AC:

92823

AN:

152160

Hom.:

28775

Cov.:

AF XY:

0.605

AC XY:

44958

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.688

AC:

28563

AN:

41532

American (AMR)

AF:

0.488

AC:

7471

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1771

AN:

3466

East Asian (EAS)

AF:

0.775

AC:

4000

AN:

5160

South Asian (SAS)

AF:

0.597

AC:

2879

AN:

4826

European-Finnish (FIN)

AF:

0.556

AC:

5895

AN:

10608

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.593

AC:

40270

AN:

67950

Other (OTH)

AF:

0.621

AC:

1313

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1941

3882

5823

7764

9705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.577

Hom.:

10293

Bravo

AF:

0.604

Asia WGS

AF:

0.638

AC:

2218

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.82

PromoterAI

-0.095

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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rs1572381

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