Menu
GeneBe

rs78627024

chr6-29828210-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.237G>A(p.Glu79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000948 in 1,613,652 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00065 ( 3 hom. )

Consequence

HLA-G
NM_001384290.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0180
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)

Genome browser will be placed here

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 6-29828210-G-A is Benign according to our data. Variant chr6-29828210-G-A is described in ClinVar as [Benign]. Clinvar id is 776116.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=-0.018 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 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HLA-GNM_001384290.1 linkuse as main transcriptc.237G>A p.Glu79= 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.237G>A p.Glu79= synonymous_variant 2/7 NM_001384290.1 P2P17693-1
HCG4P8ENST00000443049.1 linkuse as main transcriptn.155C>T non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00384
AC:
584
AN:
152232
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0127
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.00334
GnomAD3 exomes
AF:
0.00107
AC:
265
AN:
248698
Hom.:
1
AF XY:
0.000866
AC XY:
117
AN XY:
135070
show subpopulations
Gnomad AFR exome
AF:
0.0129
Gnomad AMR exome
AF:
0.000898
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000215
Gnomad OTH exome
AF:
0.000821
GnomAD4 exome
AF:
0.000647
AC:
945
AN:
1461302
Hom.:
3
Cov.:
89
AF XY:
0.000589
AC XY:
428
AN XY:
726974
show subpopulations
Gnomad4 AFR exome
AF:
0.0136
Gnomad4 AMR exome
AF:
0.00105
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000334
Gnomad4 OTH exome
AF:
0.000927
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00383
AC:
584
AN:
152350
Hom.:
6
Cov.:
33
AF XY:
0.00362
AC XY:
270
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0127
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00169
Hom.:
0
Bravo
AF:
0.00441
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000709
EpiControl
AF:
0.000356

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 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
14
Dann
Benign
0.93

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs78627024; hg19: chr6-29795987; API