chr6-19838134-C-T

Variant names:

• chr6-19838134-C-T
• rs1761265841
• NM_001546.4:c.380C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001546.4(ID4):​c.380C>T​(p.Pro127Leu) 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. P127R) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23295668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID4	NM_001546.4	c.380C>T	p.Pro127Leu	missense_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.380C>T	p.Pro127Leu	missense_variant	Exon 1 of 3	1	NM_001546.4	ENSP00000367972.3
LNC-LBCS	ENST00000432171.2	n.263+684G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1415954 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 701790

African (AFR) AF: 0.00 AC: 0 AN: 31352

American (AMR) AF: 0.00 AC: 0 AN: 38722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24948

East Asian (EAS) AF: 0.00 AC: 0 AN: 36624

South Asian (SAS) AF: 0.00 AC: 0 AN: 80968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090014

Other (OTH) AF: 0.00 AC: 0 AN: 58512

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.097	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.59
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.35
Sift	Benign	0.13	T
Sift4G	Benign	0.079	T
Polyphen		0.75	P
Vest4		0.093
MutPred		0.28		Gain of catalytic residue at P127 (P = 0.0217);
MVP		0.98
MPC		1.5
ClinPred		0.26	T
GERP RS		2.6
Varity_R		0.090
gMVP		0.53
Mutation Taster		=90/10	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

dbSNP: rs1761265841; hg19: chr6-19838365;