ENST00000425174.1:n.-238A>C

Variant names:

• chr6-31382526-T-G
• rs2844535
• ENST00000425174.1:n.-238A>C

Variant summary

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

The ENST00000425174.1(HLA-S):​n.-238A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,958 control chromosomes in the GnomAD database, including 6,239 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 0.28 (6239 hom., cov: 31)
• Consequence: HLA-S ENST00000425174.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 12 publications found

Genes affected

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

MICA-AS1 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000425174.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-S	ENST00000425174.1	TSL:6	n.-238A>C		upstream_gene	N/A
	MICA-AS1	ENST00000745027.1		n.*185A>C		downstream_gene	N/A
	MICA-AS1	ENST00000745028.1		n.*216A>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43060 AN: 151840 Hom.: 6228 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.284 AC: 43117 AN: 151958 Hom.: 6239 Cov.: 31 AF XY: 0.284 AC XY: 21072 AN XY: 74284

African (AFR) AF: 0.337 AC: 13958 AN: 41382

American (AMR) AF: 0.257 AC: 3926 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 952 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1040 AN: 5156

South Asian (SAS) AF: 0.311 AC: 1498 AN: 4824

European-Finnish (FIN) AF: 0.273 AC: 2882 AN: 10576

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17768 AN: 67968

Other (OTH) AF: 0.270 AC: 569 AN: 2110

Alfa AF: 0.162 Hom.: 340

Bravo AF: 0.281

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.0
DANN	Benign	0.54
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs2844535; hg19: chr6-31350303;