Genetic Variant NM_014424.5:c.*1615C>A (chr1-16013965-G-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_014424.5(HSPB7):c.*1615C>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,120 control chromosomes in the GnomAD database, including 29,255 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 ( 29239 hom., cov: 32)

Exomes 𝑓: 0.55 ( 16 hom. )

Consequence

HSPB7
NM_014424.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.208

Publications

18 publications found

Variant links:

COSMIC-nc: COSV61307806

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=-0.83).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014424.5. 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.*1615C>A	downstream_gene	N/A	NP_055239.1
HSPB7	NM_001349682.2		c.*1615C>A	downstream_gene	N/A	NP_001336611.1
HSPB7	NM_001349689.2		c.*1615C>A	downstream_gene	N/A	NP_001336618.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HSPB7	ENST00000311890.14	TSL:1 MANE Select	c.*1615C>A	downstream_gene	N/A	ENSP00000310111.9
HSPB7	ENST00000411503.5	TSL:1	c.*1615C>A	downstream_gene	N/A	ENSP00000391578.1
HSPB7	ENST00000442459.2	TSL:1	n.*63C>A	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93388

AN:

151900

Hom.:

29220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.626

GnomAD4 exome

AF:

0.549

AC:

AN:

102

Hom.:

AF XY:

0.527

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.553

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.615

AC:

93447

AN:

152018

Hom.:

29239

Cov.:

AF XY:

0.609

AC XY:

45243

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.704

AC:

29209

AN:

41482

American (AMR)

AF:

0.492

AC:

7521

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1773

AN:

3468

East Asian (EAS)

AF:

0.774

AC:

3982

AN:

5146

South Asian (SAS)

AF:

0.596

AC:

2871

AN:

4816

European-Finnish (FIN)

AF:

0.556

AC:

5883

AN:

10576

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.592

AC:

40232

AN:

67944

Other (OTH)

AF:

0.624

AC:

1316

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1838

3675

5513

7350

9188

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:

0.593

Hom.:

16408

Bravo

AF:

0.611

Asia WGS

AF:

0.637

AC:

2216

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.1

(source)

DANN

Benign

0.74

PhyloP100

-0.21

Mutation Taster

=98/2

polymorphism

(source)

Splicing

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