6-29827359-A-C

Variant names:

• chr6-29827359-A-C
• rs1736933
• NM_001363567.2:c.6+315A>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.6+315A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 351,580 control chromosomes in the GnomAD database, including 44,938 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 0.48 (18027 hom., cov: 31)
  • Exomes 𝑓: 0.51 (26911 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001363567.2	c.6+315A>C		intron_variant	Intron 1 of 7		NP_001350496.1
HLA-G	NM_001384280.1	c.6+315A>C		intron_variant	Intron 2 of 8		NP_001371209.1
HLA-G	NM_002127.6	c.-113+315A>C		intron_variant	Intron 1 of 7		NP_002118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000376828.6	c.6+315A>C		intron_variant	Intron 1 of 7	6		ENSP00000366024.2
HLA-G	ENST00000428701.6	n.66+315A>C		intron_variant	Intron 1 of 4	6
HLA-F-AS1	ENST00000849927.1	n.26+1112T>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73465 AN: 151530 Hom.: 18004 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.507 AC: 101388 AN: 199932 Hom.: 26911 Cov.: 0 AF XY: 0.529 AC XY: 58373 AN XY: 110420

African (AFR) AF: 0.506 AC: 2653 AN: 5238

American (AMR) AF: 0.509 AC: 5227 AN: 10260

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 2512 AN: 4374

East Asian (EAS) AF: 0.604 AC: 4934 AN: 8168

South Asian (SAS) AF: 0.668 AC: 26482 AN: 39616

European-Finnish (FIN) AF: 0.365 AC: 3248 AN: 8898

Middle Eastern (MID) AF: 0.510 AC: 1009 AN: 1980

European-Non Finnish (NFE) AF: 0.453 AC: 50604 AN: 111770

Other (OTH) AF: 0.490 AC: 4719 AN: 9628

GnomAD4 genome AF: 0.485 AC: 73529 AN: 151648 Hom.: 18027 Cov.: 31 AF XY: 0.485 AC XY: 35920 AN XY: 74112

African (AFR) AF: 0.509 AC: 21014 AN: 41284

American (AMR) AF: 0.514 AC: 7836 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1964 AN: 3462

East Asian (EAS) AF: 0.609 AC: 3120 AN: 5120

South Asian (SAS) AF: 0.666 AC: 3208 AN: 4816

European-Finnish (FIN) AF: 0.338 AC: 3561 AN: 10546

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

European-Non Finnish (NFE) AF: 0.459 AC: 31177 AN: 67866

Other (OTH) AF: 0.507 AC: 1069 AN: 2110

Alfa AF: 0.473 Hom.: 2201

Bravo AF: 0.497

Asia WGS AF: 0.684 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-1.3
PromoterAI		-0.033	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: rs1736933; hg19: chr6-29795136; COSMIC: COSV64407033;