rs1736927

Variant names:

• chr6-29828338-A-C
• rs1736927
• NM_001384290.1:c.343+22A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-29828338-A-C
• chr6-29828338-A-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.343+22A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,595,332 control chromosomes in the GnomAD database, including 228,475 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 0.56 (24088 hom., cov: 32)
  • Exomes 𝑓: 0.53 (204387 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 14 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 (SAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.343+22A>C		intron_variant	Intron 2 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.343+22A>C		intron_variant	Intron 2 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84376 AN: 151608 Hom.: 24045 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.582

GnomAD2 exomes AF: 0.550 AC: 130346 AN: 237076 AF XY: 0.557

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.594

Gnomad ASJ exome AF: 0.654

Gnomad EAS exome AF: 0.611

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.526 AC: 759085 AN: 1443606 Hom.: 204387 Cov.: 52 AF XY: 0.534 AC XY: 382476 AN XY: 716752

African (AFR) AF: 0.656 AC: 21845 AN: 33280

American (AMR) AF: 0.602 AC: 26472 AN: 43952

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 16545 AN: 25304

East Asian (EAS) AF: 0.671 AC: 26426 AN: 39410

South Asian (SAS) AF: 0.750 AC: 63476 AN: 84660

European-Finnish (FIN) AF: 0.364 AC: 18669 AN: 51270

Middle Eastern (MID) AF: 0.656 AC: 3739 AN: 5698

European-Non Finnish (NFE) AF: 0.498 AC: 548161 AN: 1100388

Other (OTH) AF: 0.566 AC: 33752 AN: 59644

GnomAD4 genome AF: 0.557 AC: 84473 AN: 151726 Hom.: 24088 Cov.: 32 AF XY: 0.555 AC XY: 41137 AN XY: 74130

African (AFR) AF: 0.650 AC: 26900 AN: 41412

American (AMR) AF: 0.608 AC: 9291 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2240 AN: 3462

East Asian (EAS) AF: 0.625 AC: 3194 AN: 5112

South Asian (SAS) AF: 0.754 AC: 3642 AN: 4828

European-Finnish (FIN) AF: 0.352 AC: 3701 AN: 10522

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33642 AN: 67798

Other (OTH) AF: 0.587 AC: 1239 AN: 2110

Alfa AF: 0.542 Hom.: 6072

Bravo AF: 0.579

Asia WGS AF: 0.741 AC: 2576 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	5.9
DANN	Benign	0.29
PhyloP100		-2.5
PromoterAI		0.013	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: rs1736927; hg19: chr6-29796115; COSMIC: COSV64405591;