1-16016759-T-C

Position:

• chr1-16016759-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014424.5(HSPB7):​c.333+315A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,412 control chromosomes in the GnomAD database, including 29,152 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 0.62 (29152 hom., cov: 28)
• Consequence: HSPB7 NM_014424.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.15

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPB7	NM_014424.5	c.333+315A>G		intron_variant		ENST00000311890.14	NP_055239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPB7	ENST00000311890.14	c.333+315A>G		intron_variant		1	NM_014424.5	ENSP00000310111.9

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93058 AN: 151296 Hom.: 29131 Cov.: 28

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.626

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.615 AC: 93119 AN: 151412 Hom.: 29152 Cov.: 28 AF XY: 0.609 AC XY: 45089 AN XY: 73982

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.625

Alfa AF: 0.605 Hom.: 3318

Bravo AF: 0.611

Asia WGS AF: 0.638 AC: 2218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs1739843; hg19: chr1-16343254;