NM_001363567.2:c.6+39C>T

Variant names:

• chr6-29827083-C-T
• rs1632946
• NM_001363567.2:c.6+39C>T

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+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 502,108 control chromosomes in the GnomAD database, including 63,816 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 (18134 hom., cov: 32)
  • Exomes 𝑓: 0.50 (45682 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831
• 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]

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 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.6+39C>T		intron	N/A	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.6+39C>T		intron	N/A	NP_001371209.1	Q5RJ85
	HLA-G	NM_002127.6		c.-113+39C>T		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.6+39C>T		intron	N/A	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000428701.6	TSL:6	n.66+39C>T		intron	N/A
	HLA-F-AS1	ENST00000849927.1		n.26+1388G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73691 AN: 151866 Hom.: 18111 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

GnomAD2 exomes AF: 0.498 AC: 97450 AN: 195746 AF XY: 0.507

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.503

Gnomad ASJ exome AF: 0.576

Gnomad EAS exome AF: 0.600

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.498

GnomAD4 exome AF: 0.499 AC: 174810 AN: 350124 Hom.: 45682 Cov.: 0 AF XY: 0.517 AC XY: 102529 AN XY: 198316

African (AFR) AF: 0.512 AC: 5053 AN: 9878

American (AMR) AF: 0.500 AC: 15656 AN: 31286

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 6351 AN: 11104

East Asian (EAS) AF: 0.604 AC: 7208 AN: 11940

South Asian (SAS) AF: 0.668 AC: 41172 AN: 61606

European-Finnish (FIN) AF: 0.342 AC: 10053 AN: 29422

Middle Eastern (MID) AF: 0.537 AC: 1513 AN: 2818

European-Non Finnish (NFE) AF: 0.454 AC: 80053 AN: 176388

Other (OTH) AF: 0.494 AC: 7751 AN: 15682

GnomAD4 genome AF: 0.485 AC: 73754 AN: 151984 Hom.: 18134 Cov.: 32 AF XY: 0.485 AC XY: 36040 AN XY: 74258

African (AFR) AF: 0.510 AC: 21119 AN: 41388

American (AMR) AF: 0.514 AC: 7855 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1970 AN: 3468

East Asian (EAS) AF: 0.610 AC: 3155 AN: 5174

South Asian (SAS) AF: 0.666 AC: 3208 AN: 4820

European-Finnish (FIN) AF: 0.341 AC: 3596 AN: 10546

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31189 AN: 67994

Other (OTH) AF: 0.506 AC: 1069 AN: 2112

Alfa AF: 0.480 Hom.: 3286

Bravo AF: 0.496

Asia WGS AF: 0.682 AC: 2374 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	1.8
DANN	Benign	0.51
PhyloP100		-0.83
PromoterAI		-0.032	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: rs1632946; hg19: chr6-29794860; COSMIC: COSV64405753; COSMIC: COSV64405753;