1-16015742-A-G

Variant names:

• chr1-16015742-A-G
• rs1739840
• NM_014424.5:c.351T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014424.5(HSPB7):​c.351T>C​(p.Thr117Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,588,860 control chromosomes in the GnomAD database, including 281,129 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 (29272 hom., cov: 33)
  • Exomes 𝑓: 0.59 (251857 hom.)
• Consequence: HSPB7 NM_014424.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.44
• Publications: 24 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP7: Synonymous conserved (PhyloP=-8.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 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.351T>C	p.Thr117Thr	synonymous	Exon 3 of 3	NP_055239.1	Q9UBY9-1
	HSPB7	NM_001349682.2		c.576T>C	p.Thr192Thr	synonymous	Exon 4 of 4	NP_001336611.1	Q8N241
	HSPB7	NM_001349689.2		c.366T>C	p.Thr122Thr	synonymous	Exon 3 of 3	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.351T>C	p.Thr117Thr	synonymous	Exon 3 of 3	ENSP00000310111.9	Q9UBY9-1
	HSPB7	ENST00000487046.1	TSL:1	c.366T>C	p.Thr122Thr	synonymous	Exon 3 of 3	ENSP00000419477.1	Q9UBY9-2
	HSPB7	ENST00000406363.2	TSL:1	c.363T>C	p.Thr121Thr	synonymous	Exon 3 of 3	ENSP00000385472.2	Q68DG0

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93453 AN: 151940 Hom.: 29251 Cov.: 33

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.625

GnomAD2 exomes AF: 0.580 AC: 138499 AN: 238962 AF XY: 0.584

Gnomad AFR exome AF: 0.702

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.753

Gnomad FIN exome AF: 0.568

Gnomad NFE exome AF: 0.594

Gnomad OTH exome AF: 0.572

GnomAD4 exome AF: 0.590 AC: 847795 AN: 1436802 Hom.: 251857 Cov.: 51 AF XY: 0.590 AC XY: 419675 AN XY: 710856

African (AFR) AF: 0.715 AC: 23630 AN: 33072

American (AMR) AF: 0.403 AC: 17642 AN: 43766

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 13014 AN: 25108

East Asian (EAS) AF: 0.729 AC: 28554 AN: 39176

South Asian (SAS) AF: 0.587 AC: 49452 AN: 84274

European-Finnish (FIN) AF: 0.564 AC: 28571 AN: 50620

Middle Eastern (MID) AF: 0.611 AC: 3400 AN: 5564

European-Non Finnish (NFE) AF: 0.591 AC: 647702 AN: 1095950

Other (OTH) AF: 0.605 AC: 35830 AN: 59272

GnomAD4 genome AF: 0.615 AC: 93514 AN: 152058 Hom.: 29272 Cov.: 33 AF XY: 0.610 AC XY: 45299 AN XY: 74302

African (AFR) AF: 0.704 AC: 29228 AN: 41500

American (AMR) AF: 0.492 AC: 7525 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1779 AN: 3466

East Asian (EAS) AF: 0.777 AC: 4000 AN: 5148

South Asian (SAS) AF: 0.597 AC: 2878 AN: 4820

European-Finnish (FIN) AF: 0.556 AC: 5875 AN: 10572

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.592 AC: 40253 AN: 67944

Other (OTH) AF: 0.623 AC: 1316 AN: 2112

Alfa AF: 0.595 Hom.: 10746

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	-1.0
CADD	Benign	0.0050
DANN	Benign	0.63
PhyloP100		-8.4
Mutation Taster		=99/1	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: rs1739840; hg19: chr1-16342237; COSMIC: COSV108143135; COSMIC: COSV108143135;