6-19837914-G-C

Variant names:

• chr6-19837914-G-C
• rs1202229052
• NM_001546.4:c.160G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001546.4(ID4):​c.160G>C​(p.Glu54Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,271,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. E54K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ID4 NM_001546.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30540958).
• BS2: High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID4	NM_001546.4	c.160G>C	p.Glu54Gln	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.160G>C	p.Glu54Gln	missense_variant	Exon 1 of 3	1	NM_001546.4	ENSP00000367972.3
LNC-LBCS	ENST00000432171.2	n.263+904C>G		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000142 AC: 18 AN: 1271874 Hom.: 0 Cov.: 32 AF XY: 0.0000112 AC XY: 7 AN XY: 624848

African (AFR) AF: 0.00 AC: 0 AN: 26250

American (AMR) AF: 0.00 AC: 0 AN: 24504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21294

East Asian (EAS) AF: 0.00 AC: 0 AN: 27114

South Asian (SAS) AF: 0.00 AC: 0 AN: 61092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4750

European-Non Finnish (NFE) AF: 0.0000178 AC: 18 AN: 1011488

Other (OTH) AF: 0.00 AC: 0 AN: 51392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.015
Eigen_PC	Benign	0.036
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.5
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.22
Sift	Benign	0.40	T
Sift4G	Benign	0.55	T
Polyphen		0.92	P
Vest4		0.12
MutPred		0.33		Gain of methylation at K51 (P = 0.1124);
MVP		0.94
MPC		0.63
ClinPred		0.49	T
GERP RS		3.1
Varity_R		0.15
gMVP		0.44
Mutation Taster		=85/15	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: rs1202229052; hg19: chr6-19838145;