rs17179108

Variant names:

• chr6-29830865-C-T
• rs17179108
• NM_001384290.1:c.*126C>T

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.*126C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 390,066 control chromosomes in the GnomAD database, including 5,502 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 0.11 (1117 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4385 hom.)
• Consequence: HLA-G NM_001384290.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 59 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.*126C>T		3_prime_UTR	Exon 7 of 7	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.*126C>T		3_prime_UTR	Exon 8 of 8	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.*126C>T		3_prime_UTR	Exon 9 of 9	NP_001371209.1	Q5RJ85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.*126C>T		3_prime_UTR	Exon 7 of 7	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.*126C>T		3_prime_UTR	Exon 8 of 8	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.*48C>T		3_prime_UTR	Exon 7 of 7	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17341 AN: 152064 Hom.: 1107 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.154 AC: 36684 AN: 237884 Hom.: 4385 Cov.: 0 AF XY: 0.162 AC XY: 21982 AN XY: 135922

African (AFR) AF: 0.145 AC: 991 AN: 6812

American (AMR) AF: 0.182 AC: 3477 AN: 19096

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 1364 AN: 8096

East Asian (EAS) AF: 0.216 AC: 1952 AN: 9056

South Asian (SAS) AF: 0.232 AC: 11489 AN: 49600

European-Finnish (FIN) AF: 0.0803 AC: 743 AN: 9252

Middle Eastern (MID) AF: 0.201 AC: 319 AN: 1584

European-Non Finnish (NFE) AF: 0.119 AC: 14686 AN: 122984

Other (OTH) AF: 0.146 AC: 1663 AN: 11404

GnomAD4 genome AF: 0.114 AC: 17373 AN: 152182 Hom.: 1117 Cov.: 32 AF XY: 0.114 AC XY: 8466 AN XY: 74394

African (AFR) AF: 0.121 AC: 5009 AN: 41502

American (AMR) AF: 0.140 AC: 2147 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1029 AN: 5166

South Asian (SAS) AF: 0.195 AC: 938 AN: 4810

European-Finnish (FIN) AF: 0.0513 AC: 544 AN: 10612

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6821 AN: 68018

Other (OTH) AF: 0.134 AC: 282 AN: 2110

Alfa AF: 0.108 Hom.: 734

Bravo AF: 0.120

Asia WGS AF: 0.195 AC: 675 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.37
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17179108; hg19: chr6-29798642; COSMIC: COSV64405197; COSMIC: COSV64405197;