11-123057914-A-G

Variant names:

• chr11-123057914-A-G
• rs4802
• NM_006597.6:c.1761T>C

Variant summary

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

The NM_006597.6(HSPA8):​c.1761T>C​(p.Ala587Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,603,014 control chromosomes in the GnomAD database, including 65,838 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 0.34 (10232 hom., cov: 32)
  • Exomes 𝑓: 0.26 (55606 hom.)
• Consequence: HSPA8 NM_006597.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 24 publications found

Genes affected

HSPA8 (HGNC:5241): (heat shock protein family A (Hsp70) member 8) This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

SNORD14E (HGNC:30354): (small nucleolar RNA, C/D box 14E)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-1.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA8	NM_006597.6	c.1761T>C	p.Ala587Ala	synonymous_variant	Exon 9 of 9	ENST00000534624.6	NP_006588.1
HSPA8	XM_011542798.2	c.1761T>C	p.Ala587Ala	synonymous_variant	Exon 9 of 9		XP_011541100.1
HSPA8	NM_153201.4	c.1388-86T>C		intron_variant	Intron 7 of 7		NP_694881.1
SNORD14E	NR_003125.2	n.*163T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6	c.1761T>C	p.Ala587Ala	synonymous_variant	Exon 9 of 9	1	NM_006597.6	ENSP00000432083.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52040 AN: 151842 Hom.: 10200 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.323 AC: 78283 AN: 242580 AF XY: 0.313

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.583

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.263 AC: 381611 AN: 1451054 Hom.: 55606 Cov.: 31 AF XY: 0.265 AC XY: 190957 AN XY: 721686

African (AFR) AF: 0.534 AC: 17635 AN: 33002

American (AMR) AF: 0.426 AC: 18149 AN: 42586

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 6049 AN: 25662

East Asian (EAS) AF: 0.576 AC: 22778 AN: 39542

South Asian (SAS) AF: 0.355 AC: 30047 AN: 84702

European-Finnish (FIN) AF: 0.234 AC: 12488 AN: 53338

Middle Eastern (MID) AF: 0.256 AC: 1460 AN: 5710

European-Non Finnish (NFE) AF: 0.231 AC: 256011 AN: 1106546

Other (OTH) AF: 0.283 AC: 16994 AN: 59966

GnomAD4 genome AF: 0.343 AC: 52131 AN: 151960 Hom.: 10232 Cov.: 32 AF XY: 0.348 AC XY: 25837 AN XY: 74268

African (AFR) AF: 0.516 AC: 21371 AN: 41408

American (AMR) AF: 0.370 AC: 5648 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3470

East Asian (EAS) AF: 0.581 AC: 3006 AN: 5170

South Asian (SAS) AF: 0.376 AC: 1814 AN: 4820

European-Finnish (FIN) AF: 0.239 AC: 2524 AN: 10552

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16026 AN: 67960

Other (OTH) AF: 0.305 AC: 645 AN: 2112

Alfa AF: 0.267 Hom.: 2033

Bravo AF: 0.362

Asia WGS AF: 0.446 AC: 1548 AN: 3478

EpiCase AF: 0.237

EpiControl AF: 0.241

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-1.4
Mutation Taster		=98/2	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: rs4802; hg19: chr11-122928622; COSMIC: COSV57082578; COSMIC: COSV57082578;