6-29828972-C-A

Variant names:

• chr6-29828972-C-A
• rs62391965
• NM_001384290.1:c.619+154C>A

Variant summary

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

The NM_001363567.2(HLA-G):​c.634+154C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 152,086 control chromosomes in the GnomAD database, including 370 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 0.052 (370 hom., cov: 31)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363567.2. 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+154C>A		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.634+154C>A		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.634+154C>A		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+154C>A		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.634+154C>A		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000936944.1		c.619+154C>A		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7883 AN: 151968 Hom.: 368 Cov.: 31

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0522

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

GnomAD4 genome AF: 0.0518 AC: 7884 AN: 152086 Hom.: 370 Cov.: 31 AF XY: 0.0542 AC XY: 4033 AN XY: 74342

African (AFR) AF: 0.0122 AC: 507 AN: 41500

American (AMR) AF: 0.0440 AC: 672 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.187 AC: 964 AN: 5150

South Asian (SAS) AF: 0.165 AC: 794 AN: 4808

European-Finnish (FIN) AF: 0.0389 AC: 413 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0607 AC: 4123 AN: 67946

Other (OTH) AF: 0.0526 AC: 111 AN: 2110

Alfa AF: 0.0421 Hom.: 25

Bravo AF: 0.0482

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.72
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs62391965; hg19: chr6-29796749;