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GeneBe

rs11807575

chr1-16015706-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_014424.5(HSPB7):c.387G>A(p.Pro129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,611,576 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 36 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 30 hom. )

Consequence

HSPB7
NM_014424.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.73
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-16015706-C-T is Benign according to our data. Variant chr1-16015706-C-T is described in ClinVar as [Benign]. Clinvar id is 787740.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.73 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1624/152306) while in subpopulation AFR AF= 0.0367 (1525/41564). AF 95% confidence interval is 0.0352. There are 36 homozygotes in gnomad4. There are 747 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 36 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HSPB7NM_014424.5 linkuse as main transcriptc.387G>A p.Pro129= synonymous_variant 3/3 ENST00000311890.14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSPB7ENST00000311890.14 linkuse as main transcriptc.387G>A p.Pro129= synonymous_variant 3/31 NM_014424.5 P3Q9UBY9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0106
AC:
1618
AN:
152188
Hom.:
36
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0367
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00419
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00908
GnomAD3 exomes
AF:
0.00282
AC:
702
AN:
248952
Hom.:
18
AF XY:
0.00203
AC XY:
273
AN XY:
134644
show subpopulations
Gnomad AFR exome
AF:
0.0386
Gnomad AMR exome
AF:
0.00163
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000986
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000801
Gnomad OTH exome
AF:
0.00148
GnomAD4 exome
AF:
0.00107
AC:
1562
AN:
1459270
Hom.:
30
Cov.:
30
AF XY:
0.000908
AC XY:
659
AN XY:
725702
show subpopulations
Gnomad4 AFR exome
AF:
0.0364
Gnomad4 AMR exome
AF:
0.00217
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000697
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000837
Gnomad4 OTH exome
AF:
0.00241
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0107
AC:
1624
AN:
152306
Hom.:
36
Cov.:
32
AF XY:
0.0100
AC XY:
747
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0367
Gnomad4 AMR
AF:
0.00418
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00899
Alfa
AF:
0.00451
Hom.:
4
Bravo
AF:
0.0123
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 03, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
0.73
Dann
Benign
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11807575; hg19: chr1-16342201; API