6-29830648-G-T

Variant names:

• chr6-29830648-G-T
• rs915669
• NM_001384290.1:c.*29-120G>T

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.*29-120G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 685,742 control chromosomes in the GnomAD database, including 103,863 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 (22797 hom., cov: 32)
  • Exomes 𝑓: 0.54 (81066 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 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.*29-120G>T		intron	N/A	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.*29-120G>T		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.*29-120G>T		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.*29-120G>T		intron	N/A	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.*29-120G>T		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.*29-198G>T		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82397 AN: 151838 Hom.: 22763 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: 0.619

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.572

GnomAD4 exome AF: 0.541 AC: 288934 AN: 533786 Hom.: 81066 Cov.: 2 AF XY: 0.553 AC XY: 160331 AN XY: 290140

African (AFR) AF: 0.621 AC: 9367 AN: 15092

American (AMR) AF: 0.623 AC: 20943 AN: 33608

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 10598 AN: 15994

East Asian (EAS) AF: 0.662 AC: 21549 AN: 32564

South Asian (SAS) AF: 0.716 AC: 42729 AN: 59692

European-Finnish (FIN) AF: 0.360 AC: 16145 AN: 44798

Middle Eastern (MID) AF: 0.640 AC: 2348 AN: 3668

European-Non Finnish (NFE) AF: 0.498 AC: 149541 AN: 300014

Other (OTH) AF: 0.554 AC: 15714 AN: 28356

GnomAD4 genome AF: 0.543 AC: 82481 AN: 151956 Hom.: 22797 Cov.: 32 AF XY: 0.540 AC XY: 40121 AN XY: 74288

African (AFR) AF: 0.614 AC: 25425 AN: 41432

American (AMR) AF: 0.600 AC: 9166 AN: 15276

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

East Asian (EAS) AF: 0.618 AC: 3187 AN: 5158

South Asian (SAS) AF: 0.695 AC: 3351 AN: 4820

European-Finnish (FIN) AF: 0.349 AC: 3693 AN: 10574

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33586 AN: 67914

Other (OTH) AF: 0.577 AC: 1218 AN: 2112

Alfa AF: 0.525 Hom.: 18529

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	-0.93
CADD	Benign	0.023
DANN	Benign	0.46
PhyloP100		-0.25
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: rs915669; hg19: chr6-29798425; COSMIC: COSV64405408;