rs1610696

Variant names:

• chr6-29831026-C-G
• rs1610696
• ENST00000376828.6:c.*287C>G

Variant summary

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

The ENST00000936944.1(HLA-G):​c.*209C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 181,036 control chromosomes in the GnomAD database, including 10,406 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 (6269 hom., cov: 33)
  • Exomes 𝑓: 0.52 (4137 hom.)
• Consequence: HLA-G ENST00000936944.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 75 publications found

Genes affected

HLA-G (HGNC:4964): (major histocompatibility complex, class I, G) HLA-G belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000936944.1. 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
	HLA-G	NM_001384290.1	MANE Select	c.*287C>G		downstream_gene	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.*287C>G		downstream_gene	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.*287C>G		downstream_gene	N/A	NP_001371209.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000376828.6	TSL:6	c.*287C>G		3_prime_UTR	Exon 8 of 8	ENSP00000366024.2
	HLA-G	ENST00000936944.1		c.*209C>G		3_prime_UTR	Exon 7 of 7	ENSP00000607003.1
	HLA-G	ENST00000376818.7	TSL:6	c.*287C>G		3_prime_UTR	Exon 6 of 6	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43264 AN: 152016 Hom.: 6265 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.518 AC: 14975 AN: 28902 Hom.: 4137 Cov.: 0 AF XY: 0.521 AC XY: 8356 AN XY: 16024

African (AFR) AF: 0.545 AC: 363 AN: 666

American (AMR) AF: 0.445 AC: 1193 AN: 2678

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 478 AN: 798

East Asian (EAS) AF: 0.206 AC: 203 AN: 986

South Asian (SAS) AF: 0.517 AC: 3314 AN: 6406

European-Finnish (FIN) AF: 0.587 AC: 383 AN: 652

Middle Eastern (MID) AF: 0.573 AC: 63 AN: 110

European-Non Finnish (NFE) AF: 0.543 AC: 8279 AN: 15244

Other (OTH) AF: 0.513 AC: 699 AN: 1362

GnomAD4 genome AF: 0.285 AC: 43293 AN: 152134 Hom.: 6269 Cov.: 33 AF XY: 0.280 AC XY: 20812 AN XY: 74372

African (AFR) AF: 0.270 AC: 11193 AN: 41508

American (AMR) AF: 0.289 AC: 4409 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3470

East Asian (EAS) AF: 0.115 AC: 598 AN: 5190

South Asian (SAS) AF: 0.297 AC: 1435 AN: 4826

European-Finnish (FIN) AF: 0.213 AC: 2248 AN: 10562

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21072 AN: 67986

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.303 Hom.: 920

Bravo AF: 0.290

Asia WGS AF: 0.191 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.48
DANN	Benign	0.49
PhyloP100		-1.9
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: rs1610696; hg19: chr6-29798803;