rs9266722

Positions:

• chr6-31382145-C-T

Variant summary

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

The ENST00000425174.1(HLA-S):​n.49-67G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 352,166 control chromosomes in the GnomAD database, including 4,839 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 0.14 (1824 hom., cov: 31)
  • Exomes 𝑓: 0.16 (3015 hom.)
• Consequence: HLA-S ENST00000425174.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

Genes affected

HLA-S (HGNC:19395): (major histocompatibility complex, class I, S (pseudogene))

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-S	ENST00000425174.1	n.49-67G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21857 AN: 151912 Hom.: 1821 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.162 AC: 32464 AN: 200136 Hom.: 3015 Cov.: 0 AF XY: 0.161 AC XY: 18338 AN XY: 114124

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.144 AC: 21877 AN: 152030 Hom.: 1824 Cov.: 31 AF XY: 0.149 AC XY: 11097 AN XY: 74330

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.149

Alfa AF: 0.113 Hom.: 996

Bravo AF: 0.145

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.3
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9266722; hg19: chr6-31349922; COSMIC: COSV69645889;