chr6-19837899-C-T

Variant names:

• chr6-19837899-C-T
• NM_001546.4:c.145C>T

Variant summary

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

The NM_001546.4(ID4):​c.145C>T​(p.Arg49Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ID4 NM_001546.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04
• Publications: 0 publications found

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)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001546.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ID4	NM_001546.4	MANE Select	c.145C>T	p.Arg49Cys	missense	Exon 1 of 3	NP_001537.1	P47928

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ID4	ENST00000378700.8	TSL:1 MANE Select	c.145C>T	p.Arg49Cys	missense	Exon 1 of 3	ENSP00000367972.3	P47928
	ID4	ENST00000867159.1		c.145C>T	p.Arg49Cys	missense	Exon 1 of 2	ENSP00000537218.1
	LNC-LBCS	ENST00000432171.2	TSL:3	n.263+919G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000166 AC: 2 AN: 1207098 Hom.: 0 Cov.: 32 AF XY: 0.00000339 AC XY: 2 AN XY: 589604

African (AFR) AF: 0.00 AC: 0 AN: 23966

American (AMR) AF: 0.00 AC: 0 AN: 13806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18118

East Asian (EAS) AF: 0.00 AC: 0 AN: 26146

South Asian (SAS) AF: 0.00 AC: 0 AN: 47502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4012

European-Non Finnish (NFE) AF: 0.00000203 AC: 2 AN: 984406

Other (OTH) AF: 0.00 AC: 0 AN: 48222

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.90	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.0
PrimateAI	Pathogenic	0.96	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.37
Sift	Benign	0.039	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.28
MutPred		0.33		Loss of methylation at R49 (P = 0.0146)
MVP		0.96
MPC		1.3
ClinPred		0.97	D
GERP RS		2.9
Varity_R		0.32
gMVP		0.56
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

hg19: chr6-19838130;