rs11823704

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-123061470-C-A
• chr11-123061470-C-G
• chr11-123061470-C-T

Variant summary

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

The NM_006597.6(HSPA8):​c.-5-141G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 678,938 control chromosomes in the GnomAD database, including 753 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 0.024 (179 hom., cov: 32)
  • Exomes 𝑓: 0.016 (574 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	NM_006597.6	MANE Select	c.-5-141G>T		intron	N/A	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.-5-141G>T		intron	N/A	NP_694881.1	P11142-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.-5-141G>T		intron	N/A	ENSP00000432083.1	P11142-1
	HSPA8	ENST00000453788.6	TSL:1	c.-5-141G>T		intron	N/A	ENSP00000404372.2	P11142-2
	HSPA8	ENST00000527983.5	TSL:1	n.145-141G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3628 AN: 152148 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0156 AC: 8208 AN: 526672 Hom.: 574 Cov.: 6 AF XY: 0.0144 AC XY: 4031 AN XY: 279108

African (AFR) AF: 0.0486 AC: 695 AN: 14308

American (AMR) AF: 0.00589 AC: 150 AN: 25474

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 206 AN: 15474

East Asian (EAS) AF: 0.177 AC: 5616 AN: 31754

South Asian (SAS) AF: 0.00482 AC: 243 AN: 50412

European-Finnish (FIN) AF: 0.00691 AC: 216 AN: 31280

Middle Eastern (MID) AF: 0.00654 AC: 17 AN: 2598

European-Non Finnish (NFE) AF: 0.00131 AC: 428 AN: 326516

Other (OTH) AF: 0.0221 AC: 637 AN: 28856

GnomAD4 genome AF: 0.0239 AC: 3638 AN: 152266 Hom.: 179 Cov.: 32 AF XY: 0.0244 AC XY: 1815 AN XY: 74456

African (AFR) AF: 0.0529 AC: 2198 AN: 41548

American (AMR) AF: 0.0119 AC: 182 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3470

East Asian (EAS) AF: 0.192 AC: 991 AN: 5164

South Asian (SAS) AF: 0.00870 AC: 42 AN: 4826

European-Finnish (FIN) AF: 0.00622 AC: 66 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 68030

Other (OTH) AF: 0.0223 AC: 47 AN: 2112

Alfa AF: 0.0100 Hom.: 178

Bravo AF: 0.0263

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.28
PhyloP100		-1.3
PromoterAI		0.026	Neutral
Mutation Taster		=100/0	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: rs11823704; hg19: chr11-122932178;