rs1048261

Positions:

• chr1-16014456-A-T

Variant summary

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

The NM_014424.5(HSPB7):​c.*1124T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,040 control chromosomes in the GnomAD database, including 38,681 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 0.71 (38674 hom., cov: 32)
  • Exomes 𝑓: 0.66 (7 hom.)
• Consequence: HSPB7 NM_014424.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPB7	NM_014424.5	c.*1124T>A		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.*1124T>A		3_prime_UTR_variant	3/3	1	NM_014424.5	ENSP00000310111	P3
HSPB7	ENST00000411503.5	c.*1124T>A		3_prime_UTR_variant	3/3	1		ENSP00000391578
HSPB7	ENST00000442459.2	n.2274T>A		non_coding_transcript_exon_variant	2/2	1
HSPB7	ENST00000375718.4	c.*1124T>A		3_prime_UTR_variant	4/4	2		ENSP00000364870

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107786 AN: 151890 Hom.: 38651 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.718

GnomAD4 exome AF: 0.656 AC: 21 AN: 32 Hom.: 7 Cov.: 0 AF XY: 0.591 AC XY: 13 AN XY: 22

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.650

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.710 AC: 107860 AN: 152008 Hom.: 38674 Cov.: 32 AF XY: 0.709 AC XY: 52648 AN XY: 74282

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.717

Alfa AF: 0.703 Hom.: 4664

Bravo AF: 0.707

Asia WGS AF: 0.794 AC: 2761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.79

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: rs1048261; hg19: chr1-16340951;