rs1461496

Positions:

• chr11-123058916-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000526686.1(HSPA8):​c.-107T>C variant causes a 5 prime UTR 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA8	NM_006597.6	c.1324-86T>C		intron_variant		ENST00000534624.6
SNORD14D	NR_001454.2	n.80T>C		non_coding_transcript_exon_variant	1/1
HSPA8	NM_153201.4	c.1324-86T>C		intron_variant
HSPA8	XM_011542798.2	c.1324-86T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA8	ENST00000534624.6	c.1324-86T>C		intron_variant		1	NM_006597.6	P1
SNORD14D	ENST00000384390.1	n.80T>C		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.930

Gnomad4 AMR exome AF: 0.644

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.624

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.632

Gnomad4 OTH exome AF: 0.642

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

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.685

Alfa AF: 0.658 Hom.: 18526

Bravo AF: 0.725

Asia WGS AF: 0.602 AC: 2091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.92
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs1461496; hg19: chr11-122929624; COSMIC: COSV57083725; COSMIC: COSV57083725;