6-29827120-G-C

Variant names:

• chr6-29827120-G-C
• rs1233334
• NM_001363567.2:c.6+76G>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+76G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 477,270 control chromosomes in the GnomAD database, including 165,025 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 0.82 (51740 hom., cov: 32)
  • Exomes 𝑓: 0.83 (113285 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 35 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)

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 (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001363567.2	c.6+76G>C		intron_variant	Intron 1 of 7		NP_001350496.1
HLA-G	NM_001384280.1	c.6+76G>C		intron_variant	Intron 2 of 8		NP_001371209.1
HLA-G	NM_002127.6	c.-113+76G>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+76G>C		intron_variant	Intron 1 of 7	6		ENSP00000366024.2
HLA-G	ENST00000428701.6	n.66+76G>C		intron_variant	Intron 1 of 4	6
HLA-F-AS1	ENST00000849927.1	n.26+1351C>G		intron_variant	Intron 1 of 3
HLA-F-AS1	ENST00000849935.1	n.230+600C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125035 AN: 152038 Hom.: 51686 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.820

GnomAD4 exome AF: 0.833 AC: 270764 AN: 325114 Hom.: 113285 AF XY: 0.840 AC XY: 154441 AN XY: 183790

African (AFR) AF: 0.828 AC: 7390 AN: 8928

American (AMR) AF: 0.841 AC: 23343 AN: 27752

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 9011 AN: 10818

East Asian (EAS) AF: 0.986 AC: 9788 AN: 9932

South Asian (SAS) AF: 0.894 AC: 53588 AN: 59960

European-Finnish (FIN) AF: 0.725 AC: 20029 AN: 27630

Middle Eastern (MID) AF: 0.804 AC: 2242 AN: 2788

European-Non Finnish (NFE) AF: 0.820 AC: 133287 AN: 162630

Other (OTH) AF: 0.824 AC: 12086 AN: 14676

GnomAD4 genome AF: 0.822 AC: 125144 AN: 152156 Hom.: 51740 Cov.: 32 AF XY: 0.822 AC XY: 61088 AN XY: 74354

African (AFR) AF: 0.826 AC: 34304 AN: 41508

American (AMR) AF: 0.831 AC: 12705 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2873 AN: 3472

East Asian (EAS) AF: 0.979 AC: 5069 AN: 5178

South Asian (SAS) AF: 0.909 AC: 4385 AN: 4824

European-Finnish (FIN) AF: 0.715 AC: 7538 AN: 10546

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55518 AN: 68016

Other (OTH) AF: 0.822 AC: 1737 AN: 2114

Alfa AF: 0.773 Hom.: 1450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-0.74
PromoterAI		-0.064	Neutral
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: rs1233334; hg19: chr6-29794897;