11-123058167-C-T

Variant names:

• chr11-123058167-C-T
• rs4936770
• NM_006597.6:c.1755+85G>A

Variant summary

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

The NM_006597.6(HSPA8):​c.1755+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 903,328 control chromosomes in the GnomAD database, including 41,730 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 0.34 (9941 hom., cov: 27)
  • Exomes 𝑓: 0.27 (31789 hom.)
• Consequence: HSPA8 NM_006597.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 16 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]

SNORD14E (HGNC:30354): (small nucleolar RNA, C/D box 14E)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 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.1755+85G>A		intron	N/A	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.1388-339G>A		intron	N/A	NP_694881.1	P11142-2
	SNORD14E	NR_003125.2		n.-11G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.1755+85G>A		intron	N/A	ENSP00000432083.1	P11142-1
	HSPA8	ENST00000227378.7	TSL:1	c.1755+85G>A		intron	N/A	ENSP00000227378.3	P11142-1
	HSPA8	ENST00000453788.6	TSL:1	c.1388-339G>A		intron	N/A	ENSP00000404372.2	P11142-2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 50907 AN: 149040 Hom.: 9910 Cov.: 27

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.272 AC: 205054 AN: 754178 Hom.: 31789 Cov.: 10 AF XY: 0.273 AC XY: 107839 AN XY: 395254

African (AFR) AF: 0.521 AC: 9566 AN: 18358

American (AMR) AF: 0.415 AC: 13472 AN: 32464

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 4328 AN: 18522

East Asian (EAS) AF: 0.576 AC: 20938 AN: 36340

South Asian (SAS) AF: 0.350 AC: 21250 AN: 60794

European-Finnish (FIN) AF: 0.229 AC: 10005 AN: 43694

Middle Eastern (MID) AF: 0.250 AC: 1029 AN: 4118

European-Non Finnish (NFE) AF: 0.227 AC: 114146 AN: 503390

Other (OTH) AF: 0.283 AC: 10320 AN: 36498

GnomAD4 genome AF: 0.342 AC: 50993 AN: 149150 Hom.: 9941 Cov.: 27 AF XY: 0.347 AC XY: 25213 AN XY: 72584

African (AFR) AF: 0.515 AC: 20768 AN: 40326

American (AMR) AF: 0.368 AC: 5498 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 824 AN: 3460

East Asian (EAS) AF: 0.583 AC: 2950 AN: 5062

South Asian (SAS) AF: 0.376 AC: 1779 AN: 4734

European-Finnish (FIN) AF: 0.240 AC: 2365 AN: 9834

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.236 AC: 15910 AN: 67558

Other (OTH) AF: 0.306 AC: 630 AN: 2058

Alfa AF: 0.295 Hom.: 3688

Bravo AF: 0.362

Asia WGS AF: 0.446 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.77
PhyloP100		-1.7
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: rs4936770; hg19: chr11-122928875; COSMIC: COSV57083402; COSMIC: COSV57083402;