Genetic Variant ID4:p.Pro118Ser (chr6-19838106-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001546.4(ID4):c.352C>T(p.Pro118Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P118A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ID4
NM_001546.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.26

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26964623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID4	NM_001546.4 link	c.352C>T	p.Pro118Ser	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.352C>T	p.Pro118Ser	missense_variant	Exon 1 of 3	1	NM_001546.4	ENSP00000367972.3		P47928
LNC-LBCS	ENST00000432171.2 link	n.263+712G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000463

AC:

AN:

215810

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1439656

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715532

African (AFR)

AF:

0.00

AC:

AN:

32322

American (AMR)

AF:

0.00

AC:

AN:

42382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25510

East Asian (EAS)

AF:

0.00

AC:

AN:

38274

South Asian (SAS)

AF:

0.00

AC:

AN:

83552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102204

Other (OTH)

AF:

0.00

AC:

AN:

59352

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00000851

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.25

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.042

MutationAssessor

Benign

0.34

PhyloP100

3.3

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.0

REVEL

Uncertain

0.37

Sift

Benign

0.086

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.28

MVP

0.92

MPC

0.63

ClinPred

0.044

GERP RS

-0.54

Varity_R

0.069

gMVP

0.47

Mutation Taster

=94/6

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