NM_001363567.2:c.7-360C>A

Variant names:

• chr6-29827476-C-A
• rs1632943
• NM_001363567.2:c.7-360C>A

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.7-360C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 364,098 control chromosomes in the GnomAD database, including 55,773 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 0.54 (22890 hom., cov: 31)
  • Exomes 𝑓: 0.55 (32883 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• 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]

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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001363567.2		c.7-360C>A		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.7-360C>A		intron	N/A	NP_001371209.1	Q5RJ85
	HLA-G	NM_002127.6		c.-112-257C>A		intron	N/A	NP_002118.1	P17693-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000376828.6	TSL:6	c.7-360C>A		intron	N/A	ENSP00000366024.2	Q5RJ85
	HCG4P8	ENST00000443049.1	TSL:6	n.889G>T		non_coding_transcript_exon	Exon 1 of 1
	HLA-G	ENST00000428701.6	TSL:6	n.67-257C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82542 AN: 151790 Hom.: 22856 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.546 AC: 115797 AN: 212190 Hom.: 32883 Cov.: 0 AF XY: 0.566 AC XY: 66569 AN XY: 117534

African (AFR) AF: 0.611 AC: 3290 AN: 5382

American (AMR) AF: 0.598 AC: 6450 AN: 10780

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 3067 AN: 4736

East Asian (EAS) AF: 0.614 AC: 5302 AN: 8640

South Asian (SAS) AF: 0.706 AC: 29512 AN: 41814

European-Finnish (FIN) AF: 0.378 AC: 3553 AN: 9390

Middle Eastern (MID) AF: 0.623 AC: 823 AN: 1320

European-Non Finnish (NFE) AF: 0.487 AC: 58342 AN: 119848

Other (OTH) AF: 0.531 AC: 5458 AN: 10280

GnomAD4 genome AF: 0.544 AC: 82626 AN: 151908 Hom.: 22890 Cov.: 31 AF XY: 0.541 AC XY: 40168 AN XY: 74224

African (AFR) AF: 0.614 AC: 25454 AN: 41464

American (AMR) AF: 0.600 AC: 9168 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2234 AN: 3468

East Asian (EAS) AF: 0.620 AC: 3166 AN: 5110

South Asian (SAS) AF: 0.696 AC: 3351 AN: 4814

European-Finnish (FIN) AF: 0.352 AC: 3706 AN: 10536

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33707 AN: 67922

Other (OTH) AF: 0.578 AC: 1219 AN: 2108

Alfa AF: 0.712 Hom.: 9284

Bravo AF: 0.563

Asia WGS AF: 0.712 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.99
DANN	Benign	0.66
PhyloP100		-0.75
PromoterAI		0.0094	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: rs1632943; hg19: chr6-29795253; COSMIC: COSV64407040;