chr1-16017812-T-C

Variant names:

• chr1-16017812-T-C
• rs145856313
• NM_014424.5:c.152A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014424.5(HSPB7):​c.152A>G​(p.Asp51Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000535 in 1,613,284 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D51N) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0030 (4 hom., cov: 34)
  • Exomes 𝑓: 0.00028 (3 hom.)
• Consequence: HSPB7 NM_014424.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.79
• Publications: 2 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009153098).
• BP6: Variant 1-16017812-T-C is Benign according to our data. Variant chr1-16017812-T-C is described in ClinVar as Benign. ClinVar VariationId is 787741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.152A>G	p.Asp51Gly	missense	Exon 1 of 3	NP_055239.1	Q9UBY9-1
	HSPB7	NM_001349682.2		c.377A>G	p.Asp126Gly	missense	Exon 2 of 4	NP_001336611.1	Q8N241
	HSPB7	NM_001349689.2		c.152A>G	p.Asp51Gly	missense	Exon 1 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.152A>G	p.Asp51Gly	missense	Exon 1 of 3	ENSP00000310111.9	Q9UBY9-1
	HSPB7	ENST00000487046.1	TSL:1	c.152A>G	p.Asp51Gly	missense	Exon 1 of 3	ENSP00000419477.1	Q9UBY9-2
	HSPB7	ENST00000406363.2	TSL:1	c.152A>G	p.Asp51Gly	missense	Exon 1 of 3	ENSP00000385472.2	Q68DG0

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 453 AN: 152152 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000766 AC: 188 AN: 245500 AF XY: 0.000555

Gnomad AFR exome AF: 0.00993

Gnomad AMR exome AF: 0.000670

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.000281 AC: 410 AN: 1461014 Hom.: 3 Cov.: 31 AF XY: 0.000242 AC XY: 176 AN XY: 726760

African (AFR) AF: 0.00867 AC: 290 AN: 33466

American (AMR) AF: 0.000695 AC: 31 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5758

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111662

Other (OTH) AF: 0.00101 AC: 61 AN: 60348

GnomAD4 genome AF: 0.00297 AC: 453 AN: 152270 Hom.: 4 Cov.: 34 AF XY: 0.00277 AC XY: 206 AN XY: 74454

African (AFR) AF: 0.0105 AC: 437 AN: 41558

American (AMR) AF: 0.000784 AC: 12 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.000702 Hom.: 0

Bravo AF: 0.00335

ExAC AF: 0.000997 AC: 121

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0092	T
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	N
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.028	D
Polyphen		0.99	D
Vest4		0.74
MVP		0.99
MPC		0.98
ClinPred		0.019	T
GERP RS		4.6
PromoterAI		-0.053	Neutral
Varity_R		0.26
gMVP		0.59
Mutation Taster		=48/52	disease causing

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: rs145856313; hg19: chr1-16344307;