Genetic Variant ID4:p.Ala57Val (chr6-19837924-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001546.4(ID4):c.170C>T(p.Ala57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. A57G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., 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: 2.46

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26109082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID4	NM_001546.4 link	c.170C>T	p.Ala57Val	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.170C>T	p.Ala57Val	missense_variant	Exon 1 of 3	1	NM_001546.4	ENSP00000367972.3		P47928
LNC-LBCS	ENST00000432171.2 link	n.263+894G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

102286

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

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

AF:

0.00

AC:

AN:

1282416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

630776

African (AFR)

AF:

0.00

AC:

AN:

26570

American (AMR)

AF:

0.00

AC:

AN:

25050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21620

East Asian (EAS)

AF:

0.00

AC:

AN:

27606

South Asian (SAS)

AF:

0.00

AC:

AN:

62766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4798

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1017620

Other (OTH)

AF:

0.00

AC:

AN:

51958

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151122

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73798

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41314

American (AMR)

AF:

0.00

AC:

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67646

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000908

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

2.5

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.46

REVEL

Benign

0.19

Sift

Benign

0.48

Sift4G

Benign

0.42

Polyphen

0.11

Vest4

0.13

MutPred

0.48

Gain of catalytic residue at A57 (P = 0.0342);

MVP

0.85

MPC

0.67

ClinPred

0.53

GERP RS

3.1

Varity_R

0.075

gMVP

0.46

Mutation Taster

=88/12

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