6-19838194-C-T

Variant names:

• chr6-19838194-C-T
• rs778404290
• NM_001546.4:c.440C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001546.4(ID4):​c.440C>T​(p.Pro147Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000291 in 1,374,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. P147Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: ID4 NM_001546.4 missense, splice_region
• Scores: Splicing: ADA: 0.01084
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.850
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29926378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID4	NM_001546.4	c.440C>T	p.Pro147Leu	missense_variant, splice_region_variant	Exon 1 of 3	ENST00000378700.8	NP_001537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ID4	ENST00000378700.8	c.440C>T	p.Pro147Leu	missense_variant, splice_region_variant	Exon 1 of 3	1	NM_001546.4	ENSP00000367972.3
LNC-LBCS	ENST00000432171.2	n.263+624G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151992 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000582

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: 0 AN: 22058 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 AF: 8.18e-7 AC: 1 AN: 1222666 Hom.: 0 Cov.: 32 AF XY: 0.00000168 AC XY: 1 AN XY: 596040

African (AFR) AF: 0.00 AC: 0 AN: 23928

American (AMR) AF: 0.00 AC: 0 AN: 10600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16726

East Asian (EAS) AF: 0.0000368 AC: 1 AN: 27184

South Asian (SAS) AF: 0.00 AC: 0 AN: 51122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4376

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1001048

Other (OTH) AF: 0.00 AC: 0 AN: 49878

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151992 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000453 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.057
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.85
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	0.37	N
REVEL	Uncertain	0.34
Sift	Benign	1.0	T
Sift4G	Benign	0.34	T
Polyphen		1.0	D
Vest4		0.10
MutPred		0.19		Gain of catalytic residue at P147 (P = 0.064);
MVP		0.94
MPC		1.5
ClinPred		0.85	D
GERP RS		2.6
Varity_R		0.11
gMVP		0.52
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.011
dbscSNV1_RF	Benign	0.064
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

dbSNP: rs778404290; hg19: chr6-19838425;