6-29830363-A-G

Variant names:

• chr6-29830363-A-G
• rs915667
• NM_001384290.1:c.1013-15A>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.1013-15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,609,026 control chromosomes in the GnomAD database, including 176,925 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 0.47 (16911 hom., cov: 31)
  • Exomes 𝑓: 0.46 (160014 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 11 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 (SAS) allele frequency at 95% confidence interval = 0.617 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.1013-15A>G		intron	N/A	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.1028-15A>G		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.1028-15A>G		intron	N/A	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.1013-15A>G		intron	N/A	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.1028-15A>G		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.1013-15A>G		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71143 AN: 151748 Hom.: 16893 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.483

GnomAD2 exomes AF: 0.480 AC: 120288 AN: 250814 AF XY: 0.488

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.489

Gnomad ASJ exome AF: 0.558

Gnomad EAS exome AF: 0.593

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.435

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.462 AC: 672564 AN: 1457160 Hom.: 160014 Cov.: 35 AF XY: 0.468 AC XY: 339349 AN XY: 725166

African (AFR) AF: 0.502 AC: 16756 AN: 33366

American (AMR) AF: 0.492 AC: 22007 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 14476 AN: 26100

East Asian (EAS) AF: 0.651 AC: 25838 AN: 39676

South Asian (SAS) AF: 0.638 AC: 55011 AN: 86164

European-Finnish (FIN) AF: 0.331 AC: 17695 AN: 53392

Middle Eastern (MID) AF: 0.523 AC: 3015 AN: 5764

European-Non Finnish (NFE) AF: 0.441 AC: 488416 AN: 1107742

Other (OTH) AF: 0.487 AC: 29350 AN: 60238

GnomAD4 genome AF: 0.469 AC: 71199 AN: 151866 Hom.: 16911 Cov.: 31 AF XY: 0.470 AC XY: 34854 AN XY: 74232

African (AFR) AF: 0.500 AC: 20722 AN: 41412

American (AMR) AF: 0.502 AC: 7660 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1908 AN: 3470

East Asian (EAS) AF: 0.603 AC: 3107 AN: 5150

South Asian (SAS) AF: 0.635 AC: 3057 AN: 4812

European-Finnish (FIN) AF: 0.321 AC: 3385 AN: 10530

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29808 AN: 67916

Other (OTH) AF: 0.486 AC: 1024 AN: 2106

Alfa AF: 0.468 Hom.: 3199

Bravo AF: 0.480

Asia WGS AF: 0.649 AC: 2259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs915667; hg19: chr6-29798140; COSMIC: COSV64405874; COSMIC: COSV64405874;