6-29828349-AC-ACC

Variant names:

• chr6-29828349-A-AC
• rs3215482
• NM_001384290.1:c.343+38dupC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001384290.1(HLA-G):​c.343+38dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,586,250 control chromosomes in the GnomAD database, including 192,606 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (19189 hom., cov: 0)
  • Exomes 𝑓: 0.48 (173417 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 7 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]

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 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.343+38dupC		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.358+38dupC		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.358+38dupC		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.343+38dupC		intron	N/A	ENSP00000353472.6
	HCG4P8	ENST00000443049.1	TSL:6	n.15dupG		non_coding_transcript_exon	Exon 1 of 1
	HLA-G	ENST00000376828.6	TSL:6	c.358+38dupC		intron	N/A	ENSP00000366024.2

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75558 AN: 151334 Hom.: 19157 Cov.: 0

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.511

GnomAD2 exomes AF: 0.498 AC: 111161 AN: 223212 AF XY: 0.507

Gnomad AFR exome AF: 0.538

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.605

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.499

GnomAD4 exome AF: 0.484 AC: 695037 AN: 1434798 Hom.: 173417 Cov.: 49 AF XY: 0.492 AC XY: 349493 AN XY: 710584

African (AFR) AF: 0.550 AC: 18190 AN: 33082

American (AMR) AF: 0.503 AC: 21835 AN: 43408

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 13934 AN: 24314

East Asian (EAS) AF: 0.660 AC: 25963 AN: 39310

South Asian (SAS) AF: 0.710 AC: 58103 AN: 81856

European-Finnish (FIN) AF: 0.344 AC: 17626 AN: 51248

Middle Eastern (MID) AF: 0.568 AC: 3206 AN: 5640

European-Non Finnish (NFE) AF: 0.461 AC: 505381 AN: 1096700

Other (OTH) AF: 0.520 AC: 30799 AN: 59240

GnomAD4 genome AF: 0.499 AC: 75636 AN: 151452 Hom.: 19189 Cov.: 0 AF XY: 0.501 AC XY: 37011 AN XY: 73940

African (AFR) AF: 0.545 AC: 22544 AN: 41332

American (AMR) AF: 0.523 AC: 7981 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1977 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3157 AN: 5080

South Asian (SAS) AF: 0.727 AC: 3494 AN: 4808

European-Finnish (FIN) AF: 0.344 AC: 3601 AN: 10466

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31200 AN: 67734

Other (OTH) AF: 0.517 AC: 1088 AN: 2106

Alfa AF: 0.396 Hom.: 1693

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48
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: rs3215482; hg19: chr6-29796126;