6-29829378-G-C

Variant names:

• chr6-29829378-G-C
• rs17875405
• NM_001384290.1:c.620-40G>C

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.635-40G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,599,266 control chromosomes in the GnomAD database, including 1,732 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 0.058 (374 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1358 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 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.620-40G>C		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.635-40G>C		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.635-40G>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.620-40G>C		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.635-40G>C		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000936944.1		c.620-40G>C		intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8780 AN: 152082 Hom.: 368 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.00733

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0723

GnomAD2 exomes AF: 0.0454 AC: 10995 AN: 242330 AF XY: 0.0425

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.0934

Gnomad ASJ exome AF: 0.0743

Gnomad EAS exome AF: 0.00386

Gnomad FIN exome AF: 0.0119

Gnomad NFE exome AF: 0.0350

Gnomad OTH exome AF: 0.0487

GnomAD4 exome AF: 0.0376 AC: 54423 AN: 1447066 Hom.: 1358 Cov.: 30 AF XY: 0.0374 AC XY: 26869 AN XY: 719010

African (AFR) AF: 0.103 AC: 3417 AN: 33136

American (AMR) AF: 0.0941 AC: 4158 AN: 44168

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 1924 AN: 25102

East Asian (EAS) AF: 0.00705 AC: 279 AN: 39586

South Asian (SAS) AF: 0.0373 AC: 3145 AN: 84326

European-Finnish (FIN) AF: 0.0126 AC: 666 AN: 52780

Middle Eastern (MID) AF: 0.0869 AC: 493 AN: 5674

European-Non Finnish (NFE) AF: 0.0343 AC: 37766 AN: 1102552

Other (OTH) AF: 0.0431 AC: 2575 AN: 59742

GnomAD4 genome AF: 0.0578 AC: 8800 AN: 152200 Hom.: 374 Cov.: 31 AF XY: 0.0551 AC XY: 4102 AN XY: 74412

African (AFR) AF: 0.104 AC: 4298 AN: 41508

American (AMR) AF: 0.0858 AC: 1312 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0773 AC: 268 AN: 3468

East Asian (EAS) AF: 0.00735 AC: 38 AN: 5170

South Asian (SAS) AF: 0.0288 AC: 139 AN: 4820

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10612

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0361 AC: 2453 AN: 68006

Other (OTH) AF: 0.0716 AC: 151 AN: 2110

Alfa AF: 0.0467 Hom.: 36

Bravo AF: 0.0670

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.3
DANN	Benign	0.53
PhyloP100		-0.84
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: rs17875405; hg19: chr6-29797155;