11-123061470-C-T

Variant names:

• chr11-123061470-C-T
• rs11823704
• NM_006597.6:c.-5-141G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006597.6(HSPA8):​c.-5-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 526,710 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA8	NM_006597.6	c.-5-141G>A		intron_variant	Intron 1 of 8	ENST00000534624.6	NP_006588.1
HSPA8	NM_153201.4	c.-5-141G>A		intron_variant	Intron 1 of 7		NP_694881.1
HSPA8	XM_011542798.2	c.-5-141G>A		intron_variant	Intron 1 of 8		XP_011541100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6	c.-5-141G>A		intron_variant	Intron 1 of 8	1	NM_006597.6	ENSP00000432083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000190 AC: 1 AN: 526710 Hom.: 0 Cov.: 6 AF XY: 0.00000358 AC XY: 1 AN XY: 279130

African (AFR) AF: 0.00 AC: 0 AN: 14310

American (AMR) AF: 0.0000393 AC: 1 AN: 25474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15476

East Asian (EAS) AF: 0.00 AC: 0 AN: 31780

South Asian (SAS) AF: 0.00 AC: 0 AN: 50412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2598

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 326520

Other (OTH) AF: 0.00 AC: 0 AN: 28860

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.94
PhyloP100		-1.3
PromoterAI		0.0078	Neutral

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: rs11823704; hg19: chr11-122932178;