rs148490812

Variant names:

• chr1-16017145-C-A
• NM_014424.5:c.262G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-16017145-C-A
• chr1-16017145-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014424.5(HSPB7):​c.262G>T​(p.Val88Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V88M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HSPB7 NM_014424.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.76

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPB7	NM_014424.5	c.262G>T	p.Val88Leu	missense_variant	Exon 2 of 3	ENST00000311890.14	NP_055239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPB7	ENST00000311890.14	c.262G>T	p.Val88Leu	missense_variant	Exon 2 of 3	1	NM_014424.5	ENSP00000310111.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461564 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.78	.;D;.;D;.;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Uncertain	2.6	.;M;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D;D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0040	D;D;D;D;D;D
Sift4G	Uncertain	0.037	D;D;D;D;D;D
Polyphen		0.93, 0.86	.;P;P;.;.;.
Vest4		0.73
MutPred		0.86		.;.;Gain of sheet (P = 0.1539);.;.;.;
MVP		0.94
MPC		0.93
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.33
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-16343640;