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GeneBe

6-29828150-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001384290.1(HLA-G):c.177G>A(p.Arg59=) 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.903
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-29828150-G-A is Benign according to our data. Variant chr6-29828150-G-A is described in ClinVar as [Benign]. Clinvar id is 774644.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.903 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HLA-GNM_001384290.1 linkuse as main transcriptc.177G>A p.Arg59= synonymous_variant 2/7 ENST00000360323.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HLA-GENST00000360323.11 linkuse as main transcriptc.177G>A p.Arg59= synonymous_variant 2/7 NM_001384290.1 P2P17693-1
HCG4P8ENST00000443049.1 linkuse as main transcriptn.215C>T non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00416
AC:
634
AN:
152234
Hom.:
3
Cov.:
33
show subpopulations
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
GnomAD3 exomes
AF:
0.00359
AC:
889
AN:
247466
Hom.:
9
AF XY:
0.00358
AC XY:
482
AN XY:
134650
show subpopulations
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 SAS exome
AF:
0.000164
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
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.00136
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.0191
Gnomad4 NFE exome
AF:
0.00287
Gnomad4 OTH exome
AF:
0.00265
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00415
AC:
633
AN:
152352
Hom.:
3
Cov.:
33
AF XY:
0.00505
AC XY:
376
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.000553
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0259
Gnomad4 NFE
AF:
0.00431
Gnomad4 OTH
AF:
0.00378
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
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
11
Dann
Benign
0.96

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs72558174; hg19: chr6-29795927; API