chr6-29828860-C-T

Variant names:

• chr6-29828860-C-T
• rs17875403
• NM_001384290.1:c.619+42C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001384290.1(HLA-G):​c.619+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,612,828 control chromosomes in the GnomAD database, including 25 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 0.0064 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (22 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384290.1. 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_001384290.1	MANE Select	c.619+42C>T		intron	N/A	NP_001371219.1
	HLA-G	NM_001363567.2		c.634+42C>T		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.634+42C>T		intron	N/A	NP_001371209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.619+42C>T		intron	N/A	ENSP00000353472.6
	HLA-G	ENST00000376828.6	TSL:6	c.634+42C>T		intron	N/A	ENSP00000366024.2
	HLA-G	ENST00000376818.7	TSL:6	c.343+544C>T		intron	N/A	ENSP00000366014.3

Frequencies

GnomAD3 genomes AF: 0.00640 AC: 974 AN: 152112 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00374

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00400 AC: 991 AN: 247844 AF XY: 0.00393

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.00423

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000417

Gnomad NFE exome AF: 0.00371

Gnomad OTH exome AF: 0.00395

GnomAD4 exome AF: 0.00354 AC: 5172 AN: 1460598 Hom.: 22 Cov.: 41 AF XY: 0.00351 AC XY: 2549 AN XY: 726682

African (AFR) AF: 0.0150 AC: 502 AN: 33466

American (AMR) AF: 0.00519 AC: 232 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0152 AC: 397 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00118 AC: 102 AN: 86234

European-Finnish (FIN) AF: 0.000338 AC: 18 AN: 53250

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5768

European-Non Finnish (NFE) AF: 0.00323 AC: 3585 AN: 1111012

Other (OTH) AF: 0.00479 AC: 289 AN: 60368

GnomAD4 genome AF: 0.00644 AC: 981 AN: 152230 Hom.: 3 Cov.: 32 AF XY: 0.00629 AC XY: 468 AN XY: 74404

African (AFR) AF: 0.0137 AC: 569 AN: 41530

American (AMR) AF: 0.00484 AC: 74 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00374 AC: 254 AN: 67992

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00658 Hom.: 1

Bravo AF: 0.00732

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.67
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17875403; hg19: chr6-29796637;