chr6-29828480-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384290.1(HLA-G):​c.344-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,575,594 control chromosomes in the GnomAD database, including 219,134 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 0.54 ( 22762 hom., cov: 30)
Exomes 𝑓: 0.52 ( 196372 hom. )

Consequence

HLA-G
NM_001384290.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.492

Publications

7 publications found
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]
HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)
HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HLA-GNM_001384290.1 linkc.344-63C>T intron_variant Intron 2 of 6 ENST00000360323.11 NP_001371219.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HLA-GENST00000360323.11 linkc.344-63C>T intron_variant Intron 2 of 6 6 NM_001384290.1 ENSP00000353472.6 P17693-1

Frequencies

GnomAD3 genomes
AF:
0.543
AC:
82206
AN:
151482
Hom.:
22728
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.613
Gnomad AMI
AF:
0.461
Gnomad AMR
AF:
0.600
Gnomad ASJ
AF:
0.646
Gnomad EAS
AF:
0.618
Gnomad SAS
AF:
0.695
Gnomad FIN
AF:
0.350
Gnomad MID
AF:
0.687
Gnomad NFE
AF:
0.495
Gnomad OTH
AF:
0.573
GnomAD4 exome
AF:
0.519
AC:
738941
AN:
1423994
Hom.:
196372
Cov.:
49
AF XY:
0.525
AC XY:
370234
AN XY:
704654
show subpopulations
African (AFR)
AF:
0.615
AC:
19916
AN:
32388
American (AMR)
AF:
0.599
AC:
24429
AN:
40778
Ashkenazi Jewish (ASJ)
AF:
0.651
AC:
15190
AN:
23324
East Asian (EAS)
AF:
0.662
AC:
26085
AN:
39392
South Asian (SAS)
AF:
0.709
AC:
56954
AN:
80382
European-Finnish (FIN)
AF:
0.360
AC:
18132
AN:
50414
Middle Eastern (MID)
AF:
0.648
AC:
3560
AN:
5496
European-Non Finnish (NFE)
AF:
0.496
AC:
542199
AN:
1093326
Other (OTH)
AF:
0.555
AC:
32476
AN:
58494
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.454
Heterozygous variant carriers
0
19024
38048
57073
76097
95121
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
16260
32520
48780
65040
81300
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.543
AC:
82290
AN:
151600
Hom.:
22762
Cov.:
30
AF XY:
0.540
AC XY:
39985
AN XY:
74032
show subpopulations
African (AFR)
AF:
0.613
AC:
25351
AN:
41322
American (AMR)
AF:
0.600
AC:
9150
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
0.646
AC:
2239
AN:
3468
East Asian (EAS)
AF:
0.617
AC:
3130
AN:
5070
South Asian (SAS)
AF:
0.695
AC:
3348
AN:
4814
European-Finnish (FIN)
AF:
0.350
AC:
3680
AN:
10526
Middle Eastern (MID)
AF:
0.677
AC:
199
AN:
294
European-Non Finnish (NFE)
AF:
0.495
AC:
33561
AN:
67842
Other (OTH)
AF:
0.578
AC:
1213
AN:
2100
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
1828
3655
5483
7310
9138
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
720
1440
2160
2880
3600
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.517
Hom.:
2648
Bravo
AF:
0.563
Asia WGS
AF:
0.712
AC:
2475
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
7.3
DANN
Benign
0.93
PhyloP100
-0.49
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1625035; hg19: chr6-29796257; COSMIC: COSV64405405; COSMIC: COSV64405405; API