11-123061657-A-C

Variant names:

• chr11-123061657-A-C
• rs4935825
• NM_006597.6:c.-5-328T>G

Variant summary

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

The NM_006597.6(HSPA8):​c.-5-328T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 384,710 control chromosomes in the GnomAD database, including 21,784 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 0.28 (7387 hom., cov: 32)
  • Exomes 𝑓: 0.33 (14397 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.29
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 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.-5-328T>G		intron	N/A	NP_006588.1
	HSPA8	NM_153201.4		c.-5-328T>G		intron	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.-5-328T>G		intron	N/A	ENSP00000432083.1
	HSPA8	ENST00000453788.6	TSL:1	c.-5-328T>G		intron	N/A	ENSP00000404372.2
	HSPA8	ENST00000527983.5	TSL:1	n.145-328T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42350 AN: 151906 Hom.: 7386 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.332 AC: 77298 AN: 232686 Hom.: 14397 Cov.: 0 AF XY: 0.329 AC XY: 41246 AN XY: 125398

African (AFR) AF: 0.0862 AC: 615 AN: 7138

American (AMR) AF: 0.224 AC: 2096 AN: 9360

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 2608 AN: 6556

East Asian (EAS) AF: 0.00124 AC: 15 AN: 12132

South Asian (SAS) AF: 0.272 AC: 9765 AN: 35892

European-Finnish (FIN) AF: 0.368 AC: 3956 AN: 10750

Middle Eastern (MID) AF: 0.403 AC: 382 AN: 948

European-Non Finnish (NFE) AF: 0.391 AC: 53690 AN: 137316

Other (OTH) AF: 0.331 AC: 4171 AN: 12594

GnomAD4 genome AF: 0.279 AC: 42352 AN: 152024 Hom.: 7387 Cov.: 32 AF XY: 0.271 AC XY: 20140 AN XY: 74302

African (AFR) AF: 0.103 AC: 4280 AN: 41476

American (AMR) AF: 0.238 AC: 3635 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3468

East Asian (EAS) AF: 0.00560 AC: 29 AN: 5180

South Asian (SAS) AF: 0.246 AC: 1187 AN: 4820

European-Finnish (FIN) AF: 0.360 AC: 3798 AN: 10550

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.394 AC: 26798 AN: 67942

Other (OTH) AF: 0.315 AC: 664 AN: 2108

Alfa AF: 0.252 Hom.: 3610

Bravo AF: 0.263

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.018
DANN	Benign	0.35
PhyloP100		-4.3
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs4935825; hg19: chr11-122932365;