ENST00000442459.2:n.1576G>C

Variant names:

• chr1-16015154-C-G
• rs1048238
• ENST00000442459.2:n.1576G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000442459.2(HSPB7):​n.1576G>C 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 0.0487 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 ENST00000442459.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• Publications: 15 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 -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.

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.*426G>C		3_prime_UTR	Exon 3 of 3	NP_055239.1
	HSPB7	NM_001349682.2		c.*426G>C		3_prime_UTR	Exon 4 of 4	NP_001336611.1
	HSPB7	NM_001349689.2		c.*426G>C		3_prime_UTR	Exon 3 of 3	NP_001336618.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB7	ENST00000442459.2	TSL:1	n.1576G>C		non_coding_transcript_exon	Exon 2 of 2
	HSPB7	ENST00000311890.14	TSL:1 MANE Select	c.*426G>C		3_prime_UTR	Exon 3 of 3	ENSP00000310111.9
	HSPB7	ENST00000411503.5	TSL:1	c.*426G>C		3_prime_UTR	Exon 3 of 3	ENSP00000391578.1

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

African (AFR) AF: 0.0196 AC: 2 AN: 102

American (AMR) AF: 0.0301 AC: 45 AN: 1494

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 7 AN: 142

East Asian (EAS) AF: 0.00 AC: 0 AN: 172

South Asian (SAS) AF: 0.00625 AC: 5 AN: 800

European-Finnish (FIN) AF: 0.0375 AC: 9 AN: 240

Middle Eastern (MID) AF: 0.0294 AC: 1 AN: 34

European-Non Finnish (NFE) AF: 0.0644 AC: 306 AN: 4754

Other (OTH) AF: 0.0495 AC: 20 AN: 404

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

African (AFR) AF: 0.0140 AC: 582 AN: 41474

American (AMR) AF: 0.0516 AC: 789 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0639 AC: 222 AN: 3472

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5152

South Asian (SAS) AF: 0.00726 AC: 35 AN: 4820

European-Finnish (FIN) AF: 0.0457 AC: 483 AN: 10570

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0740 AC: 5028 AN: 67946

Other (OTH) AF: 0.0692 AC: 146 AN: 2110

Alfa AF: 0.00523 Hom.: 6845

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1048238; hg19: chr1-16341649;