Genetic Variant HSPB7:c.*426G>A (chr1-16015154-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001349682.2(HSPB7):c.*426G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 160,088 control chromosomes in the GnomAD database, including 26,197 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 0.57 ( 25157 hom., cov: 31)

Exomes 𝑓: 0.48 ( 1040 hom. )

Consequence

HSPB7
NM_001349682.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.485

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349682.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HSPB7	NM_014424.5	MANE Select	c.*426G>A	3_prime_UTR	Exon 3 of 3	NP_055239.1
HSPB7	NM_001349682.2		c.*426G>A	3_prime_UTR	Exon 4 of 4	NP_001336611.1
HSPB7	NM_001349689.2		c.*426G>A	3_prime_UTR	Exon 3 of 3	NP_001336618.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HSPB7	ENST00000311890.14	TSL:1 MANE Select	c.*426G>A	3_prime_UTR	Exon 3 of 3	ENSP00000310111.9
HSPB7	ENST00000411503.5	TSL:1	c.*426G>A	3_prime_UTR	Exon 3 of 3	ENSP00000391578.1
HSPB7	ENST00000442459.2	TSL:1	n.1576G>A	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

85967

AN:

151846

Hom.:

25135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.775

Gnomad SAS

AF:

0.590

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.555

GnomAD4 exome

AF:

0.479

AC:

3893

AN:

8124

Hom.:

1040

Cov.:

AF XY:

0.487

AC XY:

2093

AN XY:

4294

show subpopulations

African (AFR)

AF:

0.676

AC:

AN:

102

American (AMR)

AF:

0.363

AC:

542

AN:

1492

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

AN:

142

East Asian (EAS)

AF:

0.657

AC:

113

AN:

172

South Asian (SAS)

AF:

0.540

AC:

431

AN:

798

European-Finnish (FIN)

AF:

0.496

AC:

118

AN:

238

Middle Eastern (MID)

AF:

0.529

AC:

AN:

European-Non Finnish (NFE)

AF:

0.491

AC:

2327

AN:

4740

Other (OTH)

AF:

0.532

AC:

216

AN:

406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

186

279

372

465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.566

AC:

86030

AN:

151964

Hom.:

25157

Cov.:

AF XY:

0.564

AC XY:

41884

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.690

AC:

28599

AN:

41454

American (AMR)

AF:

0.441

AC:

6730

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1557

AN:

3472

East Asian (EAS)

AF:

0.775

AC:

3991

AN:

5152

South Asian (SAS)

AF:

0.590

AC:

2842

AN:

4816

European-Finnish (FIN)

AF:

0.510

AC:

5391

AN:

10564

Middle Eastern (MID)

AF:

0.620

AC:

181

AN:

292

European-Non Finnish (NFE)

AF:

0.518

AC:

35208

AN:

67922

Other (OTH)

AF:

0.554

AC:

1169

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1843

3686

5529

7372

9215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<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:

0.504

Hom.:

6845

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.1

(source)

DANN

Benign

0.54

PhyloP100

-0.48

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over