chr1-16017882-A-G

Variant names:

• chr1-16017882-A-G
• rs74626772
• NM_014424.5:c.82T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014424.5(HSPB7):​c.82T>C​(p.Ser28Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 36)
• Consequence: HSPB7 NM_014424.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB7	NM_014424.5	MANE Select	c.82T>C	p.Ser28Pro	missense	Exon 1 of 3	NP_055239.1
	HSPB7	NM_001349689.2		c.82T>C	p.Ser28Pro	missense	Exon 1 of 3	NP_001336618.1
	HSPB7	NM_001349683.2		c.82T>C	p.Ser28Pro	missense	Exon 1 of 3	NP_001336612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPB7	ENST00000311890.14	TSL:1 MANE Select	c.82T>C	p.Ser28Pro	missense	Exon 1 of 3	ENSP00000310111.9
	HSPB7	ENST00000487046.1	TSL:1	c.82T>C	p.Ser28Pro	missense	Exon 1 of 3	ENSP00000419477.1
	HSPB7	ENST00000406363.2	TSL:1	c.82T>C	p.Ser28Pro	missense	Exon 1 of 3	ENSP00000385472.2

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.4	L
PhyloP100		1.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.38	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.014	D
Sift4G	Benign	0.070	T
Polyphen		0.68	P
Vest4		0.56
MutPred		0.17		Loss of phosphorylation at S28 (P = 9e-04)
MVP		0.98
MPC		0.68
ClinPred		0.88	D
GERP RS		4.4
PromoterAI		0.13	Neutral
Varity_R		0.16
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs74626772; hg19: chr1-16344377;