1-16016759-T-C

Variant names:

• chr1-16016759-T-C
• rs1739843
• NM_014424.5:c.333+315A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014424.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB7	NM_014424.5	MANE Select	c.333+315A>G		intron	N/A	NP_055239.1	Q9UBY9-1
	HSPB7	NM_001349682.2		c.558+315A>G		intron	N/A	NP_001336611.1	Q8N241
	HSPB7	NM_001349689.2		c.348+315A>G		intron	N/A	NP_001336618.1	Q9UBY9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB7	ENST00000311890.14	TSL:1 MANE Select	c.333+315A>G		intron	N/A	ENSP00000310111.9	Q9UBY9-1
	HSPB7	ENST00000487046.1	TSL:1	c.348+315A>G		intron	N/A	ENSP00000419477.1	Q9UBY9-2
	HSPB7	ENST00000406363.2	TSL:1	c.345+315A>G		intron	N/A	ENSP00000385472.2	Q68DG0

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

African (AFR) AF: 0.704 AC: 29048 AN: 41240

American (AMR) AF: 0.493 AC: 7514 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1778 AN: 3466

East Asian (EAS) AF: 0.776 AC: 3980 AN: 5128

South Asian (SAS) AF: 0.595 AC: 2860 AN: 4804

European-Finnish (FIN) AF: 0.557 AC: 5803 AN: 10416

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40168 AN: 67804

Other (OTH) AF: 0.625 AC: 1309 AN: 2096

Alfa AF: 0.602 Hom.: 7705

Bravo AF: 0.611

Asia WGS AF: 0.638 AC: 2218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.57
PhyloP100		-4.1
Mutation Taster		=100/0	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: rs1739843; hg19: chr1-16343254;