6-29829776-G-C

Variant names:

• chr6-29829776-G-C
• rs1632937
• NM_001384290.1:c.896-40G>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.896-40G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,601,304 control chromosomes in the GnomAD database, including 190,314 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 (18100 hom., cov: 30)
  • Exomes 𝑓: 0.48 (172214 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 11 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=-1.01).
• 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: 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.896-40G>C		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.911-40G>C		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.911-40G>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.896-40G>C		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000478355.5	TSL:6	n.978G>C		non_coding_transcript_exon	Exon 4 of 6
	HLA-G	ENST00000376828.6	TSL:6	c.911-40G>C		intron	N/A	ENSP00000366024.2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73589 AN: 151670 Hom.: 18077 Cov.: 30

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.499

GnomAD2 exomes AF: 0.497 AC: 122249 AN: 246156 AF XY: 0.506

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.599

Gnomad FIN exome AF: 0.336

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.494

GnomAD4 exome AF: 0.481 AC: 697273 AN: 1449516 Hom.: 172214 Cov.: 30 AF XY: 0.488 AC XY: 352085 AN XY: 721368

African (AFR) AF: 0.511 AC: 16951 AN: 33190

American (AMR) AF: 0.503 AC: 22222 AN: 44182

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 14599 AN: 25526

East Asian (EAS) AF: 0.655 AC: 25989 AN: 39664

South Asian (SAS) AF: 0.671 AC: 57279 AN: 85332

European-Finnish (FIN) AF: 0.346 AC: 18399 AN: 53178

Middle Eastern (MID) AF: 0.561 AC: 3212 AN: 5722

European-Non Finnish (NFE) AF: 0.461 AC: 508002 AN: 1102832

Other (OTH) AF: 0.511 AC: 30620 AN: 59890

GnomAD4 genome AF: 0.485 AC: 73653 AN: 151788 Hom.: 18100 Cov.: 30 AF XY: 0.485 AC XY: 36004 AN XY: 74204

African (AFR) AF: 0.510 AC: 21099 AN: 41340

American (AMR) AF: 0.514 AC: 7850 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1965 AN: 3466

East Asian (EAS) AF: 0.611 AC: 3136 AN: 5136

South Asian (SAS) AF: 0.667 AC: 3214 AN: 4818

European-Finnish (FIN) AF: 0.340 AC: 3592 AN: 10566

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31139 AN: 67880

Other (OTH) AF: 0.505 AC: 1066 AN: 2112

Alfa AF: 0.478 Hom.: 3191

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2382 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	8.9
DANN	Benign	0.21
PhyloP100		-0.48
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: rs1632937; hg19: chr6-29797553; COSMIC: COSV64405374; COSMIC: COSV64405374;