chr6-29827943-A-G

Variant names:

• chr6-29827943-A-G
• rs56388903
• NM_001384290.1:c.73+26A>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.73+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 1,599,422 control chromosomes in the GnomAD database, including 593,803 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 0.87 (57297 hom., cov: 29)
  • Exomes 𝑓: 0.86 (536506 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.73+26A>G		intron_variant	Intron 1 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.73+26A>G		intron_variant	Intron 1 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131483 AN: 151662 Hom.: 57237 Cov.: 29

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.904

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.881

GnomAD2 exomes AF: 0.873 AC: 204176 AN: 233904 AF XY: 0.871

Gnomad AFR exome AF: 0.897

Gnomad AMR exome AF: 0.936

Gnomad ASJ exome AF: 0.904

Gnomad EAS exome AF: 0.980

Gnomad FIN exome AF: 0.729

Gnomad NFE exome AF: 0.853

Gnomad OTH exome AF: 0.859

GnomAD4 exome AF: 0.860 AC: 1244828 AN: 1447642 Hom.: 536506 Cov.: 47 AF XY: 0.861 AC XY: 619395 AN XY: 719364

African (AFR) AF: 0.889 AC: 29434 AN: 33108

American (AMR) AF: 0.933 AC: 40286 AN: 43188

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 22747 AN: 25056

East Asian (EAS) AF: 0.986 AC: 39038 AN: 39588

South Asian (SAS) AF: 0.890 AC: 75052 AN: 84316

European-Finnish (FIN) AF: 0.737 AC: 38151 AN: 51764

Middle Eastern (MID) AF: 0.884 AC: 4507 AN: 5100

European-Non Finnish (NFE) AF: 0.853 AC: 943851 AN: 1105930

Other (OTH) AF: 0.869 AC: 51762 AN: 59592

GnomAD4 genome AF: 0.867 AC: 131599 AN: 151780 Hom.: 57297 Cov.: 29 AF XY: 0.863 AC XY: 63934 AN XY: 74116

African (AFR) AF: 0.894 AC: 37014 AN: 41416

American (AMR) AF: 0.909 AC: 13886 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3134 AN: 3472

East Asian (EAS) AF: 0.980 AC: 4962 AN: 5062

South Asian (SAS) AF: 0.880 AC: 4224 AN: 4798

European-Finnish (FIN) AF: 0.725 AC: 7634 AN: 10530

Middle Eastern (MID) AF: 0.901 AC: 263 AN: 292

European-Non Finnish (NFE) AF: 0.852 AC: 57842 AN: 67906

Other (OTH) AF: 0.883 AC: 1864 AN: 2112

Alfa AF: 0.855 Hom.: 6498

Bravo AF: 0.885

Asia WGS AF: 0.932 AC: 3242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.24
PhyloP100		-0.23
PromoterAI		0.040	Neutral
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: rs56388903; hg19: chr6-29795720; COSMIC: COSV64407006;