chr1-16015706-C-T

Variant names:

• chr1-16015706-C-T
• rs11807575
• NM_014424.5:c.387G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014424.5(HSPB7):​c.387G>A​(p.Pro129Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,611,576 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (30 hom.)
• Consequence: HSPB7 NM_014424.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.73
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-16015706-C-T is Benign according to our data. Variant chr1-16015706-C-T is described in ClinVar as Benign. ClinVar VariationId is 787740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.73 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1624/152306) while in subpopulation AFR AF = 0.0367 (1525/41564). AF 95% confidence interval is 0.0352. There are 36 homozygotes in GnomAd4. There are 747 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 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.387G>A	p.Pro129Pro	synonymous	Exon 3 of 3	NP_055239.1	Q9UBY9-1
	HSPB7	NM_001349682.2		c.612G>A	p.Pro204Pro	synonymous	Exon 4 of 4	NP_001336611.1	Q8N241
	HSPB7	NM_001349689.2		c.402G>A	p.Pro134Pro	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.387G>A	p.Pro129Pro	synonymous	Exon 3 of 3	ENSP00000310111.9	Q9UBY9-1
	HSPB7	ENST00000487046.1	TSL:1	c.402G>A	p.Pro134Pro	synonymous	Exon 3 of 3	ENSP00000419477.1	Q9UBY9-2
	HSPB7	ENST00000406363.2	TSL:1	c.399G>A	p.Pro133Pro	synonymous	Exon 3 of 3	ENSP00000385472.2	Q68DG0

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1618 AN: 152188 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

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: 0.000235

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00282 AC: 702 AN: 248952 AF XY: 0.00203

Gnomad AFR exome AF: 0.0386

Gnomad AMR exome AF: 0.00163

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000801

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00107 AC: 1562 AN: 1459270 Hom.: 30 Cov.: 30 AF XY: 0.000908 AC XY: 659 AN XY: 725702

African (AFR) AF: 0.0364 AC: 1216 AN: 33442

American (AMR) AF: 0.00217 AC: 97 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39654

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52720

Middle Eastern (MID) AF: 0.000523 AC: 3 AN: 5738

European-Non Finnish (NFE) AF: 0.0000837 AC: 93 AN: 1110712

Other (OTH) AF: 0.00241 AC: 145 AN: 60286

GnomAD4 genome AF: 0.0107 AC: 1624 AN: 152306 Hom.: 36 Cov.: 32 AF XY: 0.0100 AC XY: 747 AN XY: 74466

African (AFR) AF: 0.0367 AC: 1525 AN: 41564

American (AMR) AF: 0.00418 AC: 64 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68018

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00469 Hom.: 5

Bravo AF: 0.0123

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.73
DANN	Benign	0.93
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism

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: rs11807575; hg19: chr1-16342201;