chr6-29830156-C-T

Variant names:

• chr6-29830156-C-T
• rs1632933
• NM_001384290.1:c.1013-222C>T

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.1013-222C>T 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 152,018 control chromosomes in the GnomAD database, including 18,143 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 (18143 hom., cov: 31)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 19 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.1013-222C>T		intron	N/A	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.1028-222C>T		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.1028-222C>T		intron	N/A	NP_001371209.1	Q5RJ85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.1013-222C>T		intron	N/A	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.1028-222C>T		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.1013-222C>T		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73718 AN: 151900 Hom.: 18120 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.485 AC: 73782 AN: 152018 Hom.: 18143 Cov.: 31 AF XY: 0.485 AC XY: 36073 AN XY: 74328

African (AFR) AF: 0.510 AC: 21150 AN: 41434

American (AMR) AF: 0.514 AC: 7861 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1970 AN: 3466

East Asian (EAS) AF: 0.611 AC: 3157 AN: 5168

South Asian (SAS) AF: 0.666 AC: 3219 AN: 4832

European-Finnish (FIN) AF: 0.340 AC: 3599 AN: 10572

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

European-Non Finnish (NFE) AF: 0.459 AC: 31169 AN: 67946

Other (OTH) AF: 0.505 AC: 1066 AN: 2110

Alfa AF: 0.478 Hom.: 34665

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	-0.90
CADD	Benign	11
DANN	Benign	0.58
PhyloP100		0.16
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: rs1632933; hg19: chr6-29797933; COSMIC: COSV64407057;