Genetic Variant ID4:p.Gly19Arg (chr6-19837809-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001546.4(ID4):c.55G>C(p.Gly19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 1,134,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G19S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

ID4
NM_001546.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.406

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]

ID4 links:

LNC-LBCS (HGNC:54418): (lncRNA bladder and prostate cancer suppressor, hnRNPK interacting)

LNC-LBCS links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID4	NM_001546.4 link	c.55G>C	p.Gly19Arg	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
ID4	ENST00000378700.8 link	c.55G>C	p.Gly19Arg	missense_variant	Exon 1 of 3	1	NM_001546.4	ENSP00000367972.3		P47928
LNC-LBCS	ENST00000432171.2 link	n.263+1009C>G		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149406

Hom.:

Cov.:

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000102

AC:

AN:

984790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

463494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19258

American (AMR)

AF:

0.00

AC:

AN:

5236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10104

East Asian (EAS)

AF:

0.0000589

AC:

AN:

16976

South Asian (SAS)

AF:

0.00

AC:

AN:

18636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2370

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

859190

Other (OTH)

AF:

0.00

AC:

AN:

36724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149406

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72878

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41136

American (AMR)

AF:

0.00

AC:

AN:

14994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67192

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Benign

0.0067

Eigen_PC

Benign

-0.022

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.91

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.34

PhyloP100

0.41

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.11

REVEL

Benign

0.25

Sift

Benign

0.15

Sift4G

Benign

0.20

Polyphen

1.0

Vest4

0.23

MutPred

0.31

Gain of MoRF binding (P = 0.0021);

MVP

0.92

MPC

1.6

ClinPred

0.75

GERP RS

2.9

PromoterAI

-0.0061

Neutral

(source)

Varity_R

0.14

gMVP

0.43

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over