6-29830122-T-C

Variant names:

• chr6-29830122-T-C
• rs1632934
• NM_001384290.1:c.1012+190T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000360323.11(HLA-G):​c.1012+190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,024 control chromosomes in the GnomAD database, including 18,142 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 (18142 hom., cov: 31)
• Consequence: HLA-G ENST00000360323.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360323.11. 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.1012+190T>C		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.1027+190T>C		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.1027+190T>C		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.1012+190T>C		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.1027+190T>C		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000376818.7	TSL:6	c.736+190T>C		intron	N/A	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73721 AN: 151906 Hom.: 18119 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.485 AC: 73785 AN: 152024 Hom.: 18142 Cov.: 31 AF XY: 0.485 AC XY: 36068 AN XY: 74332

African (AFR) AF: 0.511 AC: 21166 AN: 41456

American (AMR) AF: 0.514 AC: 7853 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3151 AN: 5160

South Asian (SAS) AF: 0.667 AC: 3217 AN: 4822

European-Finnish (FIN) AF: 0.339 AC: 3591 AN: 10578

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

European-Non Finnish (NFE) AF: 0.459 AC: 31174 AN: 67938

Other (OTH) AF: 0.507 AC: 1069 AN: 2110

Alfa AF: 0.472 Hom.: 2283

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.6
DANN	Benign	0.52
PhyloP100		-0.47
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: rs1632934; hg19: chr6-29797899; COSMIC: COSV64405607; COSMIC: COSV64405607;