chr6-29829396-A-G

Variant names:

• chr6-29829396-A-G
• rs1736920
• NM_001384290.1:c.620-22A>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.620-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,607,528 control chromosomes in the GnomAD database, including 224,447 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 (22800 hom., cov: 29)
  • Exomes 𝑓: 0.52 (201647 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 18 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=-0.91).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.620-22A>G		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.635-22A>G		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.635-22A>G		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.620-22A>G		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.635-22A>G		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000376818.7	TSL:6	c.344-22A>G		intron	N/A	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82322 AN: 151488 Hom.: 22766 Cov.: 29

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.574

GnomAD2 exomes AF: 0.544 AC: 135039 AN: 248400 AF XY: 0.550

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.593

Gnomad ASJ exome AF: 0.651

Gnomad EAS exome AF: 0.603

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.520 AC: 756620 AN: 1455922 Hom.: 201647 Cov.: 41 AF XY: 0.526 AC XY: 381096 AN XY: 723932

African (AFR) AF: 0.616 AC: 20510 AN: 33310

American (AMR) AF: 0.598 AC: 26568 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 16795 AN: 25796

East Asian (EAS) AF: 0.662 AC: 26246 AN: 39632

South Asian (SAS) AF: 0.709 AC: 60955 AN: 85918

European-Finnish (FIN) AF: 0.359 AC: 19119 AN: 53244

Middle Eastern (MID) AF: 0.649 AC: 3718 AN: 5730

European-Non Finnish (NFE) AF: 0.496 AC: 549322 AN: 1107794

Other (OTH) AF: 0.556 AC: 33387 AN: 60072

GnomAD4 genome AF: 0.544 AC: 82406 AN: 151606 Hom.: 22800 Cov.: 29 AF XY: 0.541 AC XY: 40061 AN XY: 74046

African (AFR) AF: 0.615 AC: 25403 AN: 41338

American (AMR) AF: 0.601 AC: 9167 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2237 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3171 AN: 5110

South Asian (SAS) AF: 0.696 AC: 3331 AN: 4786

European-Finnish (FIN) AF: 0.352 AC: 3696 AN: 10498

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

European-Non Finnish (NFE) AF: 0.495 AC: 33571 AN: 67848

Other (OTH) AF: 0.579 AC: 1212 AN: 2094

Alfa AF: 0.533 Hom.: 4160

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	-0.91
CADD	Benign	5.5
DANN	Benign	0.55
PhyloP100		-3.0
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: rs1736920; hg19: chr6-29797173; COSMIC: COSV64405858; COSMIC: COSV64405858;