rs915670

Variant names:

• chr6-29830642-G-A
• rs915670
• NM_001384290.1:c.*29-126G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-29830642-G-A
• chr6-29830642-G-C

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.*29-126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 698,732 control chromosomes in the GnomAD database, including 27,959 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 0.27 (5482 hom., cov: 31)
  • Exomes 𝑓: 0.28 (22477 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 9 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.*29-126G>A		intron_variant	Intron 6 of 6	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.*29-126G>A		intron_variant	Intron 6 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40537 AN: 151938 Hom.: 5480 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.278 AC: 152160 AN: 546678 Hom.: 22477 Cov.: 2 AF XY: 0.282 AC XY: 83865 AN XY: 297218

African (AFR) AF: 0.264 AC: 4073 AN: 15420

American (AMR) AF: 0.285 AC: 9945 AN: 34862

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 6331 AN: 16448

East Asian (EAS) AF: 0.152 AC: 5075 AN: 33410

South Asian (SAS) AF: 0.303 AC: 18384 AN: 60586

European-Finnish (FIN) AF: 0.203 AC: 9290 AN: 45860

Middle Eastern (MID) AF: 0.300 AC: 1118 AN: 3726

European-Non Finnish (NFE) AF: 0.292 AC: 89793 AN: 307336

Other (OTH) AF: 0.281 AC: 8151 AN: 29030

GnomAD4 genome AF: 0.267 AC: 40560 AN: 152054 Hom.: 5482 Cov.: 31 AF XY: 0.262 AC XY: 19515 AN XY: 74350

African (AFR) AF: 0.257 AC: 10648 AN: 41490

American (AMR) AF: 0.276 AC: 4212 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3468

East Asian (EAS) AF: 0.109 AC: 567 AN: 5180

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4816

European-Finnish (FIN) AF: 0.193 AC: 2039 AN: 10584

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19642 AN: 67922

Other (OTH) AF: 0.268 AC: 566 AN: 2110

Alfa AF: 0.286 Hom.: 811

Bravo AF: 0.273

Asia WGS AF: 0.178 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.61
PhyloP100		2.0
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: rs915670; hg19: chr6-29798419; COSMIC: COSV64405045; COSMIC: COSV64405045;