11-123057467-A-G

Variant names:

• chr11-123057467-A-G
• rs7948948
• NM_006597.6:c.*267T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006597.6(HSPA8):​c.*267T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 335,620 control chromosomes in the GnomAD database, including 8,140 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 0.23 (4911 hom., cov: 32)
  • Exomes 𝑓: 0.17 (3229 hom.)
• Consequence: HSPA8 NM_006597.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006597.6. 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
	HSPA8	NM_006597.6	MANE Select	c.*267T>C		downstream_gene	N/A	NP_006588.1
	HSPA8	NM_153201.4		c.*267T>C		downstream_gene	N/A	NP_694881.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.*267T>C		downstream_gene	N/A	ENSP00000432083.1
	HSPA8	ENST00000227378.7	TSL:1	c.*267T>C		downstream_gene	N/A	ENSP00000227378.3
	HSPA8	ENST00000453788.6	TSL:1	c.*267T>C		downstream_gene	N/A	ENSP00000404372.2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34993 AN: 152062 Hom.: 4891 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.175 AC: 32086 AN: 183440 Hom.: 3229 Cov.: 0 AF XY: 0.177 AC XY: 16710 AN XY: 94550

African (AFR) AF: 0.395 AC: 2017 AN: 5108

American (AMR) AF: 0.191 AC: 1039 AN: 5430

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 972 AN: 6650

East Asian (EAS) AF: 0.0912 AC: 1146 AN: 12560

South Asian (SAS) AF: 0.245 AC: 2625 AN: 10736

European-Finnish (FIN) AF: 0.156 AC: 1890 AN: 12148

Middle Eastern (MID) AF: 0.186 AC: 166 AN: 894

European-Non Finnish (NFE) AF: 0.169 AC: 19915 AN: 117870

Other (OTH) AF: 0.192 AC: 2316 AN: 12044

GnomAD4 genome AF: 0.230 AC: 35062 AN: 152180 Hom.: 4911 Cov.: 32 AF XY: 0.229 AC XY: 17027 AN XY: 74420

African (AFR) AF: 0.391 AC: 16214 AN: 41500

American (AMR) AF: 0.196 AC: 2994 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3472

East Asian (EAS) AF: 0.0885 AC: 458 AN: 5178

South Asian (SAS) AF: 0.271 AC: 1308 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1625 AN: 10600

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11298 AN: 67996

Other (OTH) AF: 0.203 AC: 427 AN: 2108

Alfa AF: 0.212 Hom.: 682

Bravo AF: 0.239

Asia WGS AF: 0.202 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.30
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7948948; hg19: chr11-122928175;