rs1130355

Variant names:

• chr6-29828216-G-A
• rs1130355
• NM_001384290.1:c.243G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-29828216-G-A
• chr6-29828216-G-C
• chr6-29828216-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001384290.1(HLA-G):​c.243G>A​(p.Pro81Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,612,856 control chromosomes in the GnomAD database, including 191,972 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 0.49 (18141 hom., cov: 32)
  • Exomes 𝑓: 0.48 (173831 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 27 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.738 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.243G>A	p.Pro81Pro	synonymous_variant	Exon 2 of 7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.243G>A	p.Pro81Pro	synonymous_variant	Exon 2 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73698 AN: 151894 Hom.: 18118 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

GnomAD2 exomes AF: 0.497 AC: 123031 AN: 247652 AF XY: 0.507

Gnomad AFR exome AF: 0.511

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.599

Gnomad FIN exome AF: 0.337

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.482 AC: 703673 AN: 1460844 Hom.: 173831 Cov.: 77 AF XY: 0.489 AC XY: 355187 AN XY: 726726

African (AFR) AF: 0.512 AC: 17119 AN: 33468

American (AMR) AF: 0.504 AC: 22477 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 14989 AN: 26116

East Asian (EAS) AF: 0.655 AC: 25999 AN: 39670

South Asian (SAS) AF: 0.672 AC: 57937 AN: 86248

European-Finnish (FIN) AF: 0.344 AC: 18187 AN: 52870

Middle Eastern (MID) AF: 0.563 AC: 3245 AN: 5764

European-Non Finnish (NFE) AF: 0.461 AC: 512791 AN: 1111698

Other (OTH) AF: 0.512 AC: 30929 AN: 60370

GnomAD4 genome AF: 0.485 AC: 73762 AN: 152012 Hom.: 18141 Cov.: 32 AF XY: 0.485 AC XY: 36043 AN XY: 74282

African (AFR) AF: 0.510 AC: 21176 AN: 41492

American (AMR) AF: 0.514 AC: 7869 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3472

East Asian (EAS) AF: 0.612 AC: 3136 AN: 5126

South Asian (SAS) AF: 0.666 AC: 3212 AN: 4820

European-Finnish (FIN) AF: 0.339 AC: 3590 AN: 10576

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31148 AN: 67906

Other (OTH) AF: 0.505 AC: 1068 AN: 2114

Alfa AF: 0.479 Hom.: 7617

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2383 AN: 3478

EpiCase AF: 0.490

EpiControl AF: 0.478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.74
PromoterAI		-0.0064	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: rs1130355; hg19: chr6-29795993; COSMIC: COSV64405583;