rs72558174

Variant names:

• chr6-29828150-G-A
• rs72558174
• NM_001384290.1:c.177G>A

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.177G>A​(p.Arg59Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,613,304 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (23 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.903
• 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]

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=-0.54).
• BP6: Variant 6-29828150-G-A is Benign according to our data. Variant chr6-29828150-G-A is described in ClinVar as Benign. ClinVar VariationId is 774644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.903 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.177G>A	p.Arg59Arg	synonymous_variant	Exon 2 of 7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.177G>A	p.Arg59Arg	synonymous_variant	Exon 2 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.00416 AC: 634 AN: 152234 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00431

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00359 AC: 889 AN: 247466 AF XY: 0.00358

Gnomad AFR exome AF: 0.000582

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.00330

Gnomad OTH exome AF: 0.00412

GnomAD4 exome AF: 0.00306 AC: 4474 AN: 1460952 Hom.: 23 Cov.: 89 AF XY: 0.00304 AC XY: 2213 AN XY: 726844

African (AFR) AF: 0.000568 AC: 19 AN: 33460

American (AMR) AF: 0.00136 AC: 61 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86246

European-Finnish (FIN) AF: 0.0191 AC: 1010 AN: 52798

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5758

European-Non Finnish (NFE) AF: 0.00287 AC: 3189 AN: 1111824

Other (OTH) AF: 0.00265 AC: 160 AN: 60368

GnomAD4 genome AF: 0.00415 AC: 633 AN: 152352 Hom.: 3 Cov.: 33 AF XY: 0.00505 AC XY: 376 AN XY: 74504

African (AFR) AF: 0.000553 AC: 23 AN: 41580

American (AMR) AF: 0.00170 AC: 26 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0259 AC: 275 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00431 AC: 293 AN: 68032

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00338 Hom.: 0

Bravo AF: 0.00224

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00387

EpiControl AF: 0.00302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		-0.90
PromoterAI		0.038	Neutral
Mutation Taster		=100/0	polymorphism

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: rs72558174; hg19: chr6-29795927;