rs17179101

Variant names:

• chr6-29830857-C-A
• rs17179101
• NM_001384290.1:c.*118C>A

Variant summary

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

The NM_001384290.1(HLA-G):​c.*118C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 411,320 control chromosomes in the GnomAD database, including 2,753 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 0.052 (379 hom., cov: 32)
  • Exomes 𝑓: 0.093 (2374 hom.)
• Consequence: HLA-G NM_001384290.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 46 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384290.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.*118C>A		3_prime_UTR	Exon 7 of 7	NP_001371219.1
	HLA-G	NM_001363567.2		c.*118C>A		3_prime_UTR	Exon 8 of 8	NP_001350496.1
	HLA-G	NM_001384280.1		c.*118C>A		3_prime_UTR	Exon 9 of 9	NP_001371209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.*118C>A		3_prime_UTR	Exon 7 of 7	ENSP00000353472.6
	HLA-G	ENST00000478355.5	TSL:6	n.1257C>A		non_coding_transcript_exon	Exon 6 of 6
	HLA-G	ENST00000478519.5	TSL:6	n.*166C>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000436375.1

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7935 AN: 152090 Hom.: 375 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0527

GnomAD4 exome AF: 0.0928 AC: 24048 AN: 259112 Hom.: 2374 Cov.: 0 AF XY: 0.102 AC XY: 15120 AN XY: 147942

African (AFR) AF: 0.0130 AC: 100 AN: 7666

American (AMR) AF: 0.0476 AC: 1027 AN: 21564

Ashkenazi Jewish (ASJ) AF: 0.0687 AC: 599 AN: 8716

East Asian (EAS) AF: 0.191 AC: 1896 AN: 9912

South Asian (SAS) AF: 0.179 AC: 9353 AN: 52348

European-Finnish (FIN) AF: 0.0542 AC: 565 AN: 10430

Middle Eastern (MID) AF: 0.0720 AC: 122 AN: 1694

European-Non Finnish (NFE) AF: 0.0698 AC: 9377 AN: 134382

Other (OTH) AF: 0.0814 AC: 1009 AN: 12400

GnomAD4 genome AF: 0.0522 AC: 7941 AN: 152208 Hom.: 379 Cov.: 32 AF XY: 0.0545 AC XY: 4056 AN XY: 74424

African (AFR) AF: 0.0124 AC: 513 AN: 41534

American (AMR) AF: 0.0446 AC: 682 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.190 AC: 980 AN: 5154

South Asian (SAS) AF: 0.165 AC: 796 AN: 4816

European-Finnish (FIN) AF: 0.0391 AC: 415 AN: 10606

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0608 AC: 4138 AN: 68012

Other (OTH) AF: 0.0555 AC: 117 AN: 2110

Alfa AF: 0.0487 Hom.: 61

Bravo AF: 0.0486

Asia WGS AF: 0.162 AC: 562 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.24
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17179101; hg19: chr6-29798634; COSMIC: COSV64405703; COSMIC: COSV64405703;