rs760861421

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001546.4(ID4):​c.389C>G​(p.Thr130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000154 in 1,553,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T130I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ID4
NM_001546.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.696
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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.023963392).
BS2
High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ID4NM_001546.4 linkc.389C>G p.Thr130Ser 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.389C>G p.Thr130Ser missense_variant Exon 1 of 3 1 NM_001546.4 ENSP00000367972.3 P47928
LNC-LBCSENST00000432171.2 linkn.263+675G>C intron_variant Intron 1 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151926
Hom.:
0
Cov.:
33
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:
0.000388
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000791
AC:
13
AN:
164350
Hom.:
0
AF XY:
0.0000996
AC XY:
9
AN XY:
90358
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00101
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000147
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
22
AN:
1401890
Hom.:
0
Cov.:
32
AF XY:
0.0000144
AC XY:
10
AN XY:
693908
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000616
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151926
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74208
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000388
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ExAC
AF:
0.0000752
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.389C>G (p.T130S) alteration is located in exon 1 (coding exon 1) of the ID4 gene. This alteration results from a C to G substitution at nucleotide position 389, causing the threonine (T) at amino acid position 130 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
19
DANN
Benign
0.47
DEOGEN2
Benign
0.17
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.29
T
M_CAP
Pathogenic
0.69
D
MetaRNN
Benign
0.024
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.41
N
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.37
N
REVEL
Benign
0.16
Sift
Benign
0.71
T
Sift4G
Benign
0.78
T
Polyphen
0.0
B
Vest4
0.067
MutPred
0.17
Loss of catalytic residue at T130 (P = 0.1298);
MVP
0.75
MPC
0.55
ClinPred
0.046
T
GERP RS
-1.1
Varity_R
0.063
gMVP
0.40

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: rs760861421; hg19: chr6-19838374; API