rs1048238

Positions:

• chr1-16015154-C-G
• chr1-16015154-C-T

Variant summary

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

The ENST00000311890.14(HSPB7):​c.*426G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 160,166 control chromosomes in the GnomAD database, including 263 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 0.049 (249 hom., cov: 31)
  • Exomes 𝑓: 0.049 (14 hom.)
• Consequence: HSPB7 ENST00000311890.14 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPB7	NM_014424.5	c.*426G>C		3_prime_UTR_variant	3/3	ENST00000311890.14	NP_055239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPB7	ENST00000311890.14	c.*426G>C		3_prime_UTR_variant	3/3	1	NM_014424.5	ENSP00000310111	P3
HSPB7	ENST00000411503.5	c.*426G>C		3_prime_UTR_variant	3/3	1		ENSP00000391578
HSPB7	ENST00000442459.2	n.1576G>C		non_coding_transcript_exon_variant	2/2	1
HSPB7	ENST00000375718.4	c.*426G>C		3_prime_UTR_variant	4/4	2		ENSP00000364870

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7408 AN: 151906 Hom.: 249 Cov.: 31

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.0699

GnomAD4 exome AF: 0.0485 AC: 395 AN: 8142 Hom.: 14 Cov.: 0 AF XY: 0.0504 AC XY: 217 AN XY: 4304

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.0301

Gnomad4 ASJ exome AF: 0.0493

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00625

Gnomad4 FIN exome AF: 0.0375

Gnomad4 NFE exome AF: 0.0644

Gnomad4 OTH exome AF: 0.0495

GnomAD4 genome AF: 0.0487 AC: 7406 AN: 152024 Hom.: 249 Cov.: 31 AF XY: 0.0457 AC XY: 3394 AN XY: 74324

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0516

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00726

Gnomad4 FIN AF: 0.0457

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.0692

Alfa AF: 0.0122 Hom.: 2829

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs1048238; hg19: chr1-16341649;