ENST00000442459.2:n.45C>T

Variant names:

• chr1-16017999-G-A
• rs1572381
• ENST00000442459.2:n.45C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000442459.2(HSPB7):​n.45C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,611,614 control chromosomes in the GnomAD database, including 284,164 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 (28775 hom., cov: 35)
  • Exomes 𝑓: 0.59 (255389 hom.)
• Consequence: HSPB7 ENST00000442459.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.824
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.056).
• 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: ENST00000442459.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB7	NM_014424.5	MANE Select	c.-36C>T		5_prime_UTR	Exon 1 of 3	NP_055239.1
	HSPB7	NM_001349689.2		c.-36C>T		5_prime_UTR	Exon 1 of 3	NP_001336618.1
	HSPB7	NM_001349683.2		c.-36C>T		5_prime_UTR	Exon 1 of 3	NP_001336612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB7	ENST00000442459.2	TSL:1	n.45C>T		non_coding_transcript_exon	Exon 1 of 2
	HSPB7	ENST00000311890.14	TSL:1 MANE Select	c.-36C>T		5_prime_UTR	Exon 1 of 3	ENSP00000310111.9
	HSPB7	ENST00000487046.1	TSL:1	c.-36C>T		5_prime_UTR	Exon 1 of 3	ENSP00000419477.1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92762 AN: 152042 Hom.: 28754 Cov.: 35

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.622

GnomAD2 exomes AF: 0.576 AC: 139812 AN: 242582 AF XY: 0.581

Gnomad AFR exome AF: 0.687

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.753

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.593

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.590 AC: 860448 AN: 1459454 Hom.: 255389 Cov.: 59 AF XY: 0.590 AC XY: 428290 AN XY: 725940

African (AFR) AF: 0.699 AC: 23387 AN: 33464

American (AMR) AF: 0.403 AC: 17999 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 13440 AN: 26094

East Asian (EAS) AF: 0.729 AC: 28901 AN: 39668

South Asian (SAS) AF: 0.586 AC: 50521 AN: 86194

European-Finnish (FIN) AF: 0.565 AC: 29509 AN: 52226

Middle Eastern (MID) AF: 0.610 AC: 3494 AN: 5732

European-Non Finnish (NFE) AF: 0.591 AC: 656842 AN: 1111186

Other (OTH) AF: 0.603 AC: 36355 AN: 60266

GnomAD4 genome AF: 0.610 AC: 92823 AN: 152160 Hom.: 28775 Cov.: 35 AF XY: 0.605 AC XY: 44958 AN XY: 74372

African (AFR) AF: 0.688 AC: 28563 AN: 41532

American (AMR) AF: 0.488 AC: 7471 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1771 AN: 3466

East Asian (EAS) AF: 0.775 AC: 4000 AN: 5160

South Asian (SAS) AF: 0.597 AC: 2879 AN: 4826

European-Finnish (FIN) AF: 0.556 AC: 5895 AN: 10608

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40270 AN: 67950

Other (OTH) AF: 0.621 AC: 1313 AN: 2116

Alfa AF: 0.577 Hom.: 10293

Bravo AF: 0.604

Asia WGS AF: 0.638 AC: 2218 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		0.82
PromoterAI		-0.095	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1572381; hg19: chr1-16344494; COSMIC: COSV58891064; COSMIC: COSV58891064;