dbSNP rs1048261: HSPB7:n.2274T>A (chr1-16014456-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000442459.2(HSPB7):n.2274T>A 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 0.71 in 152,040 control chromosomes in the GnomAD database, including 38,681 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 0.71 ( 38674 hom., cov: 32)

Exomes 𝑓: 0.66 ( 7 hom. )

Consequence

HSPB7
ENST00000442459.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.340

Publications

17 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPB7	NM_014424.5 link	c.*1124T>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000311890.14	NP_055239.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
HSPB7	ENST00000442459.2 link	n.2274T>A	non_coding_transcript_exon_variant	Exon 2 of 2	1
HSPB7	ENST00000311890.14 link	c.*1124T>A	3_prime_UTR_variant	Exon 3 of 3	1	NM_014424.5	ENSP00000310111.9
HSPB7	ENST00000411503.5 link	c.*1124T>A	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000391578.1
HSPB7	ENST00000375718.4 link	c.*1124T>A	3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000364870.4

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107786

AN:

151890

Hom.:

38651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.769

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.649

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.975

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.713

Gnomad NFE

AF:

0.678

Gnomad OTH

AF:

0.718

GnomAD4 exome

AF:

0.656

AC:

AN:

Hom.:

Cov.:

AF XY:

0.591

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.650

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.710

AC:

107860

AN:

152008

Hom.:

38674

Cov.:

AF XY:

0.709

AC XY:

52648

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.769

AC:

31900

AN:

41460

American (AMR)

AF:

0.649

AC:

9922

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

2044

AN:

3468

East Asian (EAS)

AF:

0.975

AC:

5034

AN:

5162

South Asian (SAS)

AF:

0.640

AC:

3084

AN:

4822

European-Finnish (FIN)

AF:

0.718

AC:

7580

AN:

10554

Middle Eastern (MID)

AF:

0.716

AC:

209

AN:

292

European-Non Finnish (NFE)

AF:

0.678

AC:

46050

AN:

67940

Other (OTH)

AF:

0.717

AC:

1511

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1566

3132

4697

6263

7829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.703

Hom.:

4664

Bravo

AF:

0.707

Asia WGS

AF:

0.794

AC:

2761

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.7

(source)

DANN

Benign

0.79

PhyloP100

-0.34

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over