rs41302367

Variant names:

• chr11-123061474-G-A
• rs41302367
• NM_006597.6:c.-5-145C>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.-5-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 661,116 control chromosomes in the GnomAD database, including 2,179 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 0.074 (1213 hom., cov: 32)
  • Exomes 𝑓: 0.024 (966 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 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.-5-145C>T		intron	N/A	NP_006588.1
	HSPA8	NM_153201.4		c.-5-145C>T		intron	N/A	NP_694881.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11182 AN: 152096 Hom.: 1200 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00288

Gnomad OTH AF: 0.0512

GnomAD4 exome AF: 0.0239 AC: 12164 AN: 508902 Hom.: 966 Cov.: 6 AF XY: 0.0279 AC XY: 7542 AN XY: 270068

African (AFR) AF: 0.235 AC: 3244 AN: 13820

American (AMR) AF: 0.0169 AC: 402 AN: 23790

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 189 AN: 15040

East Asian (EAS) AF: 0.0104 AC: 328 AN: 31668

South Asian (SAS) AF: 0.127 AC: 6239 AN: 49148

European-Finnish (FIN) AF: 0.0000324 AC: 1 AN: 30854

Middle Eastern (MID) AF: 0.0336 AC: 83 AN: 2470

European-Non Finnish (NFE) AF: 0.00252 AC: 791 AN: 313858

Other (OTH) AF: 0.0314 AC: 887 AN: 28254

GnomAD4 genome AF: 0.0738 AC: 11234 AN: 152214 Hom.: 1213 Cov.: 32 AF XY: 0.0742 AC XY: 5523 AN XY: 74426

African (AFR) AF: 0.231 AC: 9586 AN: 41478

American (AMR) AF: 0.0306 AC: 468 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.0193 AC: 100 AN: 5180

South Asian (SAS) AF: 0.149 AC: 717 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00287 AC: 195 AN: 68038

Other (OTH) AF: 0.0507 AC: 107 AN: 2112

Alfa AF: 0.0443 Hom.: 86

Bravo AF: 0.0801

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.67
PhyloP100		-0.51
PromoterAI		0.048	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: rs41302367; hg19: chr11-122932182;