rs17840762

Variant names:

• chr9-125241708-G-A
• rs17840762
• ENST00000468244.3:n.46G>A

Variant summary

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

The ENST00000468244.3(HSPA5-DT):​n.46G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 158,532 control chromosomes in the GnomAD database, including 1,138 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 0.11 (1106 hom., cov: 32)
  • Exomes 𝑓: 0.087 (32 hom.)
• Consequence: HSPA5-DT ENST00000468244.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 5 publications found

Genes affected

HSPA5-DT (HGNC:55645): (HSPA5 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA5-DT	NR_186826.1	n.53G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA5-DT	ENST00000468244.3	n.46G>A		non_coding_transcript_exon_variant	Exon 1 of 4	4
HSPA5-DT	ENST00000761981.1	n.72G>A		non_coding_transcript_exon_variant	Exon 1 of 3
HSPA5-DT	ENST00000761982.1	n.40G>A		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16542 AN: 152036 Hom.: 1106 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0961

GnomAD4 exome AF: 0.0872 AC: 557 AN: 6384 Hom.: 32 Cov.: 0 AF XY: 0.0871 AC XY: 297 AN XY: 3410

African (AFR) AF: 0.235 AC: 40 AN: 170

American (AMR) AF: 0.0313 AC: 3 AN: 96

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 29 AN: 240

East Asian (EAS) AF: 0.148 AC: 78 AN: 528

South Asian (SAS) AF: 0.0899 AC: 39 AN: 434

European-Finnish (FIN) AF: 0.103 AC: 64 AN: 620

Middle Eastern (MID) AF: 0.105 AC: 4 AN: 38

European-Non Finnish (NFE) AF: 0.0706 AC: 277 AN: 3926

Other (OTH) AF: 0.0693 AC: 23 AN: 332

GnomAD4 genome AF: 0.109 AC: 16569 AN: 152148 Hom.: 1106 Cov.: 32 AF XY: 0.111 AC XY: 8226 AN XY: 74374

African (AFR) AF: 0.188 AC: 7777 AN: 41460

American (AMR) AF: 0.0603 AC: 922 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3470

East Asian (EAS) AF: 0.154 AC: 794 AN: 5166

South Asian (SAS) AF: 0.119 AC: 575 AN: 4828

European-Finnish (FIN) AF: 0.0973 AC: 1031 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0707 AC: 4809 AN: 68018

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.128 Hom.: 330

Bravo AF: 0.110

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.23
DANN	Benign	0.92
PhyloP100		-1.0
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17840762; hg19: chr9-128003987;