6-19837926-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001546.4(ID4):​c.172G>C​(p.Asp58His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,437,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D58N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

ID4
NM_001546.4 missense

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.12

Publications

0 publications found
Variant links:
Genes affected
ID4 (HGNC:5363): (inhibitor of DNA binding 4) This gene encodes a member of the inhibitor of DNA binding (ID) protein family. The encoded protein lacks DNA binding ability, and instead regulates gene expression through binding to and inhibiting basic helix-loop-helix transcription factors. This protein has been implicated in the regulation of diverse cellular processes that play a role in development and tumorigenesis. [provided by RefSeq, Aug 2017]
LNC-LBCS (HGNC:54418): (lncRNA bladder and prostate cancer suppressor, hnRNPK interacting)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3921625).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ID4NM_001546.4 linkc.172G>C p.Asp58His missense_variant Exon 1 of 3 ENST00000378700.8 NP_001537.1 P47928

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ID4ENST00000378700.8 linkc.172G>C p.Asp58His missense_variant Exon 1 of 3 1 NM_001546.4 ENSP00000367972.3 P47928
LNC-LBCSENST00000432171.2 linkn.263+892C>G intron_variant Intron 1 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.00000661
AC:
1
AN:
151300
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.78e-7
AC:
1
AN:
1285668
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
632574
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26756
American (AMR)
AF:
0.00
AC:
0
AN:
25212
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21678
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27934
South Asian (SAS)
AF:
0.00
AC:
0
AN:
62964
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
44886
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5032
European-Non Finnish (NFE)
AF:
9.81e-7
AC:
1
AN:
1019082
Other (OTH)
AF:
0.00
AC:
0
AN:
52124
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151408
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
73988
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41478
American (AMR)
AF:
0.00
AC:
0
AN:
15218
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5164
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10212
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.0000148
AC:
1
AN:
67726
Other (OTH)
AF:
0.00
AC:
0
AN:
2104
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Benign
0.00031
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.34
T
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.10
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.39
T
M_CAP
Pathogenic
0.95
D
MetaRNN
Benign
0.39
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.69
N
PhyloP100
3.1
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.29
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.82
P
Vest4
0.20
MutPred
0.39
Loss of disorder (P = 0.1115);
MVP
0.98
MPC
1.4
ClinPred
0.69
D
GERP RS
2.2
Varity_R
0.23
gMVP
0.48
Mutation Taster
=82/18
polymorphism

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: rs557291472; hg19: chr6-19838157; API