11-123062819-A-G

Variant names:

• chr11-123062819-A-G
• rs2236660
• ENST00000525624.5:c.-75T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000525624.5(HSPA8):​c.-75T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,394 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 (1473 hom., cov: 33)
  • Exomes 𝑓: 0.056 (2 hom.)
• Consequence: HSPA8 ENST00000525624.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902775	XR_007062927.1	n.158A>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000525624.5	c.-75T>C		5_prime_UTR_variant	Exon 1 of 4	5		ENSP00000435154.1
ENSG00000288061	ENST00000690490.2	n.224A>G		non_coding_transcript_exon_variant	Exon 1 of 1
ENSG00000288061	ENST00000660892.2	n.43+122A>G		intron_variant	Intron 1 of 2
HSPA8	ENST00000532780.5	n.-150T>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16351 AN: 151916 Hom.: 1460 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0822

GnomAD4 exome AF: 0.0556 AC: 20 AN: 360 Hom.: 2 Cov.: 0 AF XY: 0.0582 AC XY: 17 AN XY: 292

Gnomad4 AFR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0430

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.108 AC: 16403 AN: 152034 Hom.: 1473 Cov.: 33 AF XY: 0.109 AC XY: 8104 AN XY: 74300

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0785

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0427

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0660 Hom.: 225

Bravo AF: 0.115

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.8
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2236660; hg19: chr11-122933527;