6-29828991-T-C

Variant names:

• chr6-29828991-T-C
• rs1632940
• NM_001384290.1:c.619+173T>C

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.619+173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 151,722 control chromosomes in the GnomAD database, including 44,260 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 0.76 (44260 hom., cov: 29)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.619+173T>C		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.634+173T>C		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.634+173T>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.619+173T>C		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.634+173T>C		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000376818.7	TSL:6	c.344-427T>C		intron	N/A	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115487 AN: 151604 Hom.: 44229 Cov.: 29

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.762 AC: 115562 AN: 151722 Hom.: 44260 Cov.: 29 AF XY: 0.761 AC XY: 56404 AN XY: 74138

African (AFR) AF: 0.707 AC: 29221 AN: 41352

American (AMR) AF: 0.768 AC: 11724 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2698 AN: 3460

East Asian (EAS) AF: 0.963 AC: 4933 AN: 5124

South Asian (SAS) AF: 0.838 AC: 4021 AN: 4798

European-Finnish (FIN) AF: 0.708 AC: 7459 AN: 10542

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 52979 AN: 67860

Other (OTH) AF: 0.755 AC: 1594 AN: 2112

Alfa AF: 0.777 Hom.: 14168

Bravo AF: 0.764

Asia WGS AF: 0.888 AC: 3089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.21
PhyloP100		-1.0
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: rs1632940; hg19: chr6-29796768;