rs11218942

Positions:

• chr11-123063042-C-A
• chr11-123063042-C-G
• chr11-123063042-C-T

Variant summary

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

The XR_007062927.1(LOC124902775):​n.381C>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 0.0639 in 152,200 control chromosomes in the GnomAD database, including 371 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 0.064 (371 hom., cov: 33)
  • Exomes 𝑓: 0.031 (0 hom.)
• Consequence: LOC124902775 XR_007062927.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

LOC124902775 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902775	XR_007062927.1	n.381C>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000660892.2	n.44-289C>A		intron_variant, non_coding_transcript_variant
HSPA8	ENST00000525624.5	c.-298G>T		5_prime_UTR_variant	1/4	5
	ENST00000690490.2	n.447C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9707 AN: 152050 Hom.: 371 Cov.: 33

Gnomad AFR AF: 0.0563

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0776

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0520

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0632

GnomAD4 exome AF: 0.0313 AC: 1 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.0333 AC XY: 1 AN XY: 30

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0639 AC: 9719 AN: 152168 Hom.: 371 Cov.: 33 AF XY: 0.0682 AC XY: 5071 AN XY: 74400

Gnomad4 AFR AF: 0.0563

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0776

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0527

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0644

Alfa AF: 0.0178 Hom.: 11

Bravo AF: 0.0727

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.66
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11218942; hg19: chr11-122933750;