6-29830256-G-A

Variant names:

• chr6-29830256-G-A
• rs17179080
• NM_001384290.1:c.1013-122G>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.1013-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,111,360 control chromosomes in the GnomAD database, including 316 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 0.027 (129 hom., cov: 31)
  • Exomes 𝑓: 0.012 (187 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 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.1013-122G>A		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.1028-122G>A		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.1028-122G>A		intron	N/A	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.1013-122G>A		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.1028-122G>A		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000376818.7	TSL:6	c.737-122G>A		intron	N/A	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4110 AN: 152064 Hom.: 127 Cov.: 31

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0330

GnomAD4 exome AF: 0.0121 AC: 11602 AN: 959178 Hom.: 187 AF XY: 0.0116 AC XY: 5782 AN XY: 498440

African (AFR) AF: 0.0759 AC: 1761 AN: 23212

American (AMR) AF: 0.0236 AC: 1029 AN: 43520

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 332 AN: 22636

East Asian (EAS) AF: 0.00145 AC: 54 AN: 37252

South Asian (SAS) AF: 0.00369 AC: 277 AN: 75012

European-Finnish (FIN) AF: 0.00155 AC: 82 AN: 52942

Middle Eastern (MID) AF: 0.0328 AC: 157 AN: 4788

European-Non Finnish (NFE) AF: 0.0109 AC: 7174 AN: 656250

Other (OTH) AF: 0.0169 AC: 736 AN: 43566

GnomAD4 genome AF: 0.0271 AC: 4124 AN: 152182 Hom.: 129 Cov.: 31 AF XY: 0.0263 AC XY: 1958 AN XY: 74412

African (AFR) AF: 0.0670 AC: 2780 AN: 41494

American (AMR) AF: 0.0307 AC: 469 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4820

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 719 AN: 67984

Other (OTH) AF: 0.0327 AC: 69 AN: 2110

Alfa AF: 0.0172 Hom.: 4

Bravo AF: 0.0321

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

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: rs17179080; hg19: chr6-29798033;