rs915668

Variant names:

• chr6-29830682-C-G
• rs915668
• NM_001384290.1:c.*29-86C>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.*29-86C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,036 control chromosomes in the GnomAD database, including 22,848 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 (22848 hom., cov: 32)
  • Exomes 𝑓: 0.55 (73258 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 17 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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.675 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.*29-86C>G		intron	N/A	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.*29-86C>G		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.*29-86C>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.*29-86C>G		intron	N/A	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.*29-86C>G		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.*29-164C>G		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82500 AN: 151918 Hom.: 22814 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.571

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.549 AC: 256619 AN: 467484 Hom.: 73258 Cov.: 0 AF XY: 0.563 AC XY: 142644 AN XY: 253508

African (AFR) AF: 0.629 AC: 8552 AN: 13586

American (AMR) AF: 0.646 AC: 19250 AN: 29818

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 9511 AN: 14030

East Asian (EAS) AF: 0.654 AC: 17877 AN: 27350

South Asian (SAS) AF: 0.726 AC: 42232 AN: 58142

European-Finnish (FIN) AF: 0.365 AC: 14065 AN: 38582

Middle Eastern (MID) AF: 0.650 AC: 2211 AN: 3404

European-Non Finnish (NFE) AF: 0.501 AC: 129327 AN: 258054

Other (OTH) AF: 0.554 AC: 13594 AN: 24518

GnomAD4 genome AF: 0.543 AC: 82584 AN: 152036 Hom.: 22848 Cov.: 32 AF XY: 0.541 AC XY: 40175 AN XY: 74328

African (AFR) AF: 0.614 AC: 25444 AN: 41458

American (AMR) AF: 0.600 AC: 9171 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2235 AN: 3466

East Asian (EAS) AF: 0.619 AC: 3200 AN: 5168

South Asian (SAS) AF: 0.695 AC: 3356 AN: 4828

European-Finnish (FIN) AF: 0.351 AC: 3710 AN: 10572

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33635 AN: 67942

Other (OTH) AF: 0.576 AC: 1215 AN: 2110

Alfa AF: 0.514 Hom.: 2506

Bravo AF: 0.563

Asia WGS AF: 0.712 AC: 2475 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	8.0
DANN	Benign	0.23
PhyloP100		0.016
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: rs915668; hg19: chr6-29798459; COSMIC: COSV64405412;