6-29827336-C-G

Variant names:

• chr6-29827336-C-G
• rs17875393
• NM_001363567.2:c.6+292C>G

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.6+292C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 355,956 control chromosomes in the GnomAD database, including 396 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 0.045 (231 hom., cov: 32)
  • Exomes 𝑓: 0.032 (165 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 4 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]

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

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 (AFR) allele frequency at 95% confidence interval = 0.0784 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_001363567.2		c.6+292C>G		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.6+292C>G		intron	N/A	NP_001371209.1
	HLA-G	NM_002127.6		c.-113+292C>G		intron	N/A	NP_002118.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000376828.6	TSL:6	c.6+292C>G		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000428701.6	TSL:6	n.66+292C>G		intron	N/A
	HLA-F-AS1	ENST00000849927.1		n.26+1135G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6783 AN: 152094 Hom.: 225 Cov.: 32

Gnomad AFR AF: 0.0807

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00750

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0521

GnomAD4 exome AF: 0.0315 AC: 6422 AN: 203744 Hom.: 165 Cov.: 0 AF XY: 0.0314 AC XY: 3545 AN XY: 113024

African (AFR) AF: 0.0834 AC: 440 AN: 5276

American (AMR) AF: 0.0697 AC: 741 AN: 10626

Ashkenazi Jewish (ASJ) AF: 0.0448 AC: 198 AN: 4420

East Asian (EAS) AF: 0.00335 AC: 28 AN: 8356

South Asian (SAS) AF: 0.0346 AC: 1399 AN: 40428

European-Finnish (FIN) AF: 0.0130 AC: 117 AN: 9024

Middle Eastern (MID) AF: 0.0885 AC: 156 AN: 1762

European-Non Finnish (NFE) AF: 0.0266 AC: 3032 AN: 114046

Other (OTH) AF: 0.0317 AC: 311 AN: 9806

GnomAD4 genome AF: 0.0447 AC: 6801 AN: 152212 Hom.: 231 Cov.: 32 AF XY: 0.0427 AC XY: 3178 AN XY: 74438

African (AFR) AF: 0.0807 AC: 3350 AN: 41510

American (AMR) AF: 0.0630 AC: 963 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3468

East Asian (EAS) AF: 0.00752 AC: 39 AN: 5186

South Asian (SAS) AF: 0.0274 AC: 132 AN: 4826

European-Finnish (FIN) AF: 0.0102 AC: 108 AN: 10606

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0284 AC: 1931 AN: 68000

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0344 Hom.: 11

Bravo AF: 0.0517

Asia WGS AF: 0.0240 AC: 84 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	3.9
DANN	Benign	0.47
PhyloP100		-0.23
PromoterAI		0.024	Neutral
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: rs17875393; hg19: chr6-29795113;