rs1461496

Variant names:

• chr11-123058916-A-G
• rs1461496
• ENST00000526686.1:c.-107T>C

Variant summary

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

The ENST00000526686.1(HSPA8):​c.-107T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,428,906 control chromosomes in the GnomAD database, including 300,336 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 0.71 (39732 hom., cov: 33)
  • Exomes 𝑓: 0.64 (260604 hom.)
• Consequence: HSPA8 ENST00000526686.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 15 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]

SNORD14D (HGNC:30353): (small nucleolar RNA, C/D box 14D)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526686.1. 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.1324-86T>C		intron	N/A	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.1324-86T>C		intron	N/A	NP_694881.1	P11142-2
	SNORD14D	NR_001454.2		n.80T>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000526686.1	TSL:1	c.-107T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000435019.1	E9PM13
	HSPA8	ENST00000526686.1	TSL:1	c.-107T>C		5_prime_UTR	Exon 1 of 3	ENSP00000435019.1	E9PM13
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.1324-86T>C		intron	N/A	ENSP00000432083.1	P11142-1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107901 AN: 152092 Hom.: 39675 Cov.: 33

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.684

GnomAD4 exome AF: 0.636 AC: 812399 AN: 1276696 Hom.: 260604 Cov.: 17 AF XY: 0.635 AC XY: 407542 AN XY: 641550

African (AFR) AF: 0.930 AC: 27734 AN: 29820

American (AMR) AF: 0.644 AC: 26050 AN: 40458

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 15359 AN: 24242

East Asian (EAS) AF: 0.578 AC: 22218 AN: 38426

South Asian (SAS) AF: 0.624 AC: 50475 AN: 80950

European-Finnish (FIN) AF: 0.602 AC: 31329 AN: 52014

Middle Eastern (MID) AF: 0.670 AC: 3615 AN: 5398

European-Non Finnish (NFE) AF: 0.632 AC: 600902 AN: 951278

Other (OTH) AF: 0.642 AC: 34717 AN: 54110

GnomAD4 genome AF: 0.710 AC: 108020 AN: 152210 Hom.: 39732 Cov.: 33 AF XY: 0.704 AC XY: 52398 AN XY: 74400

African (AFR) AF: 0.922 AC: 38294 AN: 41554

American (AMR) AF: 0.644 AC: 9848 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2216 AN: 3472

East Asian (EAS) AF: 0.589 AC: 3053 AN: 5180

South Asian (SAS) AF: 0.625 AC: 3018 AN: 4830

European-Finnish (FIN) AF: 0.599 AC: 6351 AN: 10594

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42939 AN: 67976

Other (OTH) AF: 0.685 AC: 1448 AN: 2114

Alfa AF: 0.661 Hom.: 26142

Bravo AF: 0.725

Asia WGS AF: 0.602 AC: 2091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		1.7
PromoterAI		0.0021	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
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: rs1461496; hg19: chr11-122929624; COSMIC: COSV57083725; COSMIC: COSV57083725;