6-29830972-C-G

Variant names:

• chr6-29830972-C-G
• rs1063320
• NM_001384290.1:c.*233C>G

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.*233C>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 0.622 in 213,126 control chromosomes in the GnomAD database, including 43,149 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 0.54 (22873 hom., cov: 33)
  • Exomes 𝑓: 0.82 (20276 hom.)
• Consequence: HLA-G NM_001384290.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 208 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 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.*233C>G		3_prime_UTR	Exon 7 of 7	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.*233C>G		3_prime_UTR	Exon 8 of 8	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.*233C>G		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.*233C>G		3_prime_UTR	Exon 7 of 7	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.*233C>G		3_prime_UTR	Exon 8 of 8	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.*155C>G		3_prime_UTR	Exon 7 of 7	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82554 AN: 151940 Hom.: 22839 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.819 AC: 49985 AN: 61068 Hom.: 20276 Cov.: 0 AF XY: 0.834 AC XY: 28780 AN XY: 34498

African (AFR) AF: 0.867 AC: 1532 AN: 1768

American (AMR) AF: 0.805 AC: 3848 AN: 4780

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 1461 AN: 1656

East Asian (EAS) AF: 0.841 AC: 2029 AN: 2414

South Asian (SAS) AF: 0.922 AC: 13282 AN: 14400

European-Finnish (FIN) AF: 0.736 AC: 1117 AN: 1518

Middle Eastern (MID) AF: 0.875 AC: 210 AN: 240

European-Non Finnish (NFE) AF: 0.770 AC: 24172 AN: 31378

Other (OTH) AF: 0.801 AC: 2334 AN: 2914

GnomAD4 genome AF: 0.543 AC: 82638 AN: 152058 Hom.: 22873 Cov.: 33 AF XY: 0.541 AC XY: 40195 AN XY: 74326

African (AFR) AF: 0.614 AC: 25473 AN: 41466

American (AMR) AF: 0.600 AC: 9179 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2238 AN: 3470

East Asian (EAS) AF: 0.618 AC: 3205 AN: 5182

South Asian (SAS) AF: 0.695 AC: 3352 AN: 4822

European-Finnish (FIN) AF: 0.351 AC: 3702 AN: 10552

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33648 AN: 67964

Other (OTH) AF: 0.579 AC: 1220 AN: 2108

Alfa AF: 0.505 Hom.: 2333

Bravo AF: 0.563

Asia WGS AF: 0.711 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.40
PhyloP100		-0.46
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: rs1063320; hg19: chr6-29798749;