dbSNP rs1354776592: ID4:p.Leu62Val (chr6-19837938-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001546.4(ID4):c.184C>G(p.Leu62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000087 in 1,494,860 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

ID4
NM_001546.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.49

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID4	NM_001546.4 link	c.184C>G	p.Leu62Val	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.184C>G	p.Leu62Val	missense_variant	Exon 1 of 3	1	NM_001546.4	ENSP00000367972.3		P47928
LNC-LBCS	ENST00000432171.2 link	n.263+880G>C		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

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

GnomAD4 exome

AF:

0.00000521

AC:

AN:

1343314

Hom.:

Cov.:

AF XY:

0.00000753

AC XY:

AN XY:

663904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27894

American (AMR)

AF:

0.00

AC:

AN:

29790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22894

East Asian (EAS)

AF:

0.0000332

AC:

AN:

30092

South Asian (SAS)

AF:

0.00

AC:

AN:

72738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5374

European-Non Finnish (NFE)

AF:

0.00000571

AC:

AN:

1051506

Other (OTH)

AF:

0.00

AC:

AN:

55008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151546

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

74020

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41378

American (AMR)

AF:

0.000394

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67850

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 07, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.184C>G (p.L62V) 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 184, causing the leucine (L) at amino acid position 62 to be replaced by a valine (V). 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

0.15

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.26

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.76

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.69

PhyloP100

3.5

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.30

Sift

Benign

0.21

Sift4G

Benign

0.48

Polyphen

0.94

Vest4

0.34

MutPred

0.42

Loss of disorder (P = 0.2005);

MVP

0.91

MPC

0.88

ClinPred

0.55

GERP RS

3.0

Varity_R

0.23

gMVP

0.41

Mutation Taster

=89/11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1354776592

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over