rs2236659

Variant names:

• chr11-123062473-A-G
• rs2236659
• ENST00000532780.5:n.197T>C

Variant summary

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

The ENST00000532780.5(HSPA8):​n.197T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,232 control chromosomes in the GnomAD database, including 1,475 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 0.11 (1475 hom., cov: 33)
  • Exomes 𝑓: 0.039 (0 hom.)
• Consequence: HSPA8 ENST00000532780.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 9 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]

ENSG00000288061 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000532780.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000532780.5	TSL:2	n.197T>C		non_coding_transcript_exon	Exon 1 of 4
	ENSG00000288061	ENST00000836650.1		n.176A>G		non_coding_transcript_exon	Exon 1 of 2
	HSPA8	ENST00000525624.5	TSL:5	c.-6+277T>C		intron	N/A	ENSP00000435154.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16375 AN: 152038 Hom.: 1462 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0821

GnomAD4 exome AF: 0.0395 AC: 3 AN: 76 Hom.: 0 Cov.: 0 AF XY: 0.0313 AC XY: 2 AN XY: 64

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 16

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0385 AC: 2 AN: 52

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.108 AC: 16427 AN: 152156 Hom.: 1475 Cov.: 33 AF XY: 0.109 AC XY: 8120 AN XY: 74396

African (AFR) AF: 0.235 AC: 9749 AN: 41512

American (AMR) AF: 0.0787 AC: 1203 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3470

East Asian (EAS) AF: 0.195 AC: 1002 AN: 5142

South Asian (SAS) AF: 0.194 AC: 936 AN: 4832

European-Finnish (FIN) AF: 0.0322 AC: 342 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0427 AC: 2903 AN: 67980

Other (OTH) AF: 0.0812 AC: 171 AN: 2106

Alfa AF: 0.0856 Hom.: 134

Bravo AF: 0.115

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		-0.17
PromoterAI		0.021	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2236659; hg19: chr11-122933181;