NM_001384290.1:c.372C>T

Variant names:

• chr6-29828571-C-T
• rs79303923
• NM_001384290.1:c.372C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001384290.1(HLA-G):​c.372C>T​(p.Gly124Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,612,976 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (24 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.362
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 6-29828571-C-T is Benign according to our data. Variant chr6-29828571-C-T is described in ClinVar as Benign. ClinVar VariationId is 782473.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.362 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 24 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_001384290.1	MANE Select	c.372C>T	p.Gly124Gly	synonymous	Exon 3 of 7	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.387C>T	p.Gly129Gly	synonymous	Exon 4 of 8	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.387C>T	p.Gly129Gly	synonymous	Exon 5 of 9	NP_001371209.1	Q5RJ85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.372C>T	p.Gly124Gly	synonymous	Exon 3 of 7	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.387C>T	p.Gly129Gly	synonymous	Exon 4 of 8	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.372C>T	p.Gly124Gly	synonymous	Exon 3 of 7	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 535 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00562

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00366

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00225 AC: 557 AN: 247052 AF XY: 0.00209

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.00275

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00321

Gnomad OTH exome AF: 0.00263

GnomAD4 exome AF: 0.00418 AC: 6103 AN: 1460648 Hom.: 24 Cov.: 53 AF XY: 0.00410 AC XY: 2982 AN XY: 726650

African (AFR) AF: 0.00454 AC: 152 AN: 33480

American (AMR) AF: 0.00271 AC: 121 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.000134 AC: 7 AN: 52314

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.00496 AC: 5510 AN: 1111908

Other (OTH) AF: 0.00502 AC: 303 AN: 60376

GnomAD4 genome AF: 0.00351 AC: 535 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00297 AC XY: 221 AN XY: 74486

African (AFR) AF: 0.00560 AC: 233 AN: 41580

American (AMR) AF: 0.00314 AC: 48 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00366 AC: 249 AN: 68034

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00378 Hom.: 1

Bravo AF: 0.00417

EpiCase AF: 0.00387

EpiControl AF: 0.00326

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.6
DANN	Benign	0.81
PhyloP100		0.36
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs79303923; hg19: chr6-29796348;