chr6-29830833-C-T

Variant names:

• chr6-29830833-C-T
• rs1707
• NM_001384290.1:c.*94C>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.*94C>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 0.889 in 431,992 control chromosomes in the GnomAD database, including 171,406 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 0.87 (57840 hom., cov: 29)
  • Exomes 𝑓: 0.90 (113566 hom.)
• Consequence: HLA-G NM_001384290.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 60 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.*94C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.*94C>T		3_prime_UTR_variant	Exon 7 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132142 AN: 151790 Hom.: 57781 Cov.: 29

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.884

GnomAD4 exome AF: 0.899 AC: 251746 AN: 280084 Hom.: 113566 Cov.: 0 AF XY: 0.903 AC XY: 143957 AN XY: 159364

African (AFR) AF: 0.929 AC: 7711 AN: 8302

American (AMR) AF: 0.954 AC: 22684 AN: 23770

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 8236 AN: 8746

East Asian (EAS) AF: 0.978 AC: 11546 AN: 11800

South Asian (SAS) AF: 0.926 AC: 50108 AN: 54098

European-Finnish (FIN) AF: 0.782 AC: 9911 AN: 12678

Middle Eastern (MID) AF: 0.908 AC: 1488 AN: 1638

European-Non Finnish (NFE) AF: 0.880 AC: 128269 AN: 145696

Other (OTH) AF: 0.883 AC: 11793 AN: 13356

GnomAD4 genome AF: 0.871 AC: 132258 AN: 151908 Hom.: 57840 Cov.: 29 AF XY: 0.866 AC XY: 64294 AN XY: 74248

African (AFR) AF: 0.906 AC: 37530 AN: 41404

American (AMR) AF: 0.910 AC: 13904 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3128 AN: 3466

East Asian (EAS) AF: 0.980 AC: 5053 AN: 5154

South Asian (SAS) AF: 0.880 AC: 4227 AN: 4804

European-Finnish (FIN) AF: 0.725 AC: 7652 AN: 10558

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57861 AN: 67934

Other (OTH) AF: 0.885 AC: 1863 AN: 2104

Alfa AF: 0.871 Hom.: 15340

Bravo AF: 0.889

Asia WGS AF: 0.932 AC: 3240 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.8
DANN	Benign	0.30
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1707; hg19: chr6-29798610;