6-29829209-G-A

Variant names:

• chr6-29829209-G-A
• rs1632938
• NM_001384290.1:c.620-209G>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.620-209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,260 control chromosomes in the GnomAD database, including 18,114 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 0.49 (18114 hom., cov: 30)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 8 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 (SAS) allele frequency at 95% confidence interval = 0.653 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.620-209G>A		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.635-209G>A		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.635-209G>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.620-209G>A		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.635-209G>A		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000376818.7	TSL:6	c.344-209G>A		intron	N/A	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73613 AN: 151144 Hom.: 18091 Cov.: 30

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.487 AC: 73677 AN: 151260 Hom.: 18114 Cov.: 30 AF XY: 0.487 AC XY: 36014 AN XY: 73920

African (AFR) AF: 0.513 AC: 21107 AN: 41182

American (AMR) AF: 0.518 AC: 7853 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1969 AN: 3448

East Asian (EAS) AF: 0.612 AC: 3137 AN: 5122

South Asian (SAS) AF: 0.672 AC: 3212 AN: 4780

European-Finnish (FIN) AF: 0.341 AC: 3587 AN: 10526

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31159 AN: 67736

Other (OTH) AF: 0.507 AC: 1060 AN: 2090

Alfa AF: 0.472 Hom.: 6045

Bravo AF: 0.496

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.57
PhyloP100		-2.5
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: rs1632938; hg19: chr6-29796986; COSMIC: COSV64406307; COSMIC: COSV64406307;