11-123057926-A-T

Variant names:

• chr11-123057926-A-T
• rs3763897
• NM_006597.6:c.1756-7T>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.1756-7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,588,350 control chromosomes in the GnomAD database, including 1,028 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.021 (101 hom., cov: 32)
  • Exomes 𝑓: 0.024 (927 hom.)
• Consequence: HSPA8 NM_006597.6 splice_region, intron
• Scores: Splicing: ADA: 0.0001606
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 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.1756-7T>A		splice_region intron	N/A	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.1388-98T>A		intron	N/A	NP_694881.1	P11142-2
	SNORD14E	NR_003125.2		n.*151T>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.1756-7T>A		splice_region intron	N/A	ENSP00000432083.1	P11142-1
	HSPA8	ENST00000227378.7	TSL:1	c.1756-7T>A		splice_region intron	N/A	ENSP00000227378.3	P11142-1
	HSPA8	ENST00000453788.6	TSL:1	c.1388-98T>A		intron	N/A	ENSP00000404372.2	P11142-2

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3158 AN: 152132 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0369 AC: 8339 AN: 225842 AF XY: 0.0359

Gnomad AFR exome AF: 0.00387

Gnomad AMR exome AF: 0.0591

Gnomad ASJ exome AF: 0.00700

Gnomad EAS exome AF: 0.172

Gnomad FIN exome AF: 0.0198

Gnomad NFE exome AF: 0.0166

Gnomad OTH exome AF: 0.0224

GnomAD4 exome AF: 0.0237 AC: 33980 AN: 1436100 Hom.: 927 Cov.: 30 AF XY: 0.0241 AC XY: 17233 AN XY: 713834

African (AFR) AF: 0.00264 AC: 85 AN: 32150

American (AMR) AF: 0.0549 AC: 2126 AN: 38744

Ashkenazi Jewish (ASJ) AF: 0.00573 AC: 141 AN: 24622

East Asian (EAS) AF: 0.165 AC: 6528 AN: 39450

South Asian (SAS) AF: 0.0458 AC: 3793 AN: 82738

European-Finnish (FIN) AF: 0.0188 AC: 996 AN: 53050

Middle Eastern (MID) AF: 0.00532 AC: 30 AN: 5636

European-Non Finnish (NFE) AF: 0.0172 AC: 18926 AN: 1100486

Other (OTH) AF: 0.0229 AC: 1355 AN: 59224

GnomAD4 genome AF: 0.0207 AC: 3159 AN: 152250 Hom.: 101 Cov.: 32 AF XY: 0.0223 AC XY: 1658 AN XY: 74436

African (AFR) AF: 0.00390 AC: 162 AN: 41558

American (AMR) AF: 0.0303 AC: 463 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.171 AC: 884 AN: 5174

South Asian (SAS) AF: 0.0439 AC: 212 AN: 4824

European-Finnish (FIN) AF: 0.0174 AC: 185 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0176 AC: 1200 AN: 68012

Other (OTH) AF: 0.0133 AC: 28 AN: 2108

Alfa AF: 0.0154 Hom.: 3

Bravo AF: 0.0216

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.67
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.010
SpliceAI score (max)		0.020		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: rs3763897; hg19: chr11-122928634; COSMIC: COSV57086253; COSMIC: COSV57086253;