6-19837918-C-G

Variant names:

• chr6-19837918-C-G
• rs772859582
• NM_001546.4:c.164C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001546.4(ID4):​c.164C>G​(p.Ala55Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000784 in 1,275,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A55V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: ID4 NM_001546.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28152815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID4	NM_001546.4	c.164C>G	p.Ala55Gly	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.164C>G	p.Ala55Gly	missense_variant	Exon 1 of 3	1	NM_001546.4	ENSP00000367972.3
LNC-LBCS	ENST00000432171.2	n.263+900G>C		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.84e-7 AC: 1 AN: 1275834 Hom.: 0 Cov.: 32 AF XY: 0.00000159 AC XY: 1 AN XY: 627024

African (AFR) AF: 0.0000379 AC: 1 AN: 26364

American (AMR) AF: 0.00 AC: 0 AN: 24680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21384

East Asian (EAS) AF: 0.00 AC: 0 AN: 27266

South Asian (SAS) AF: 0.00 AC: 0 AN: 61774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4818

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1013680

Other (OTH) AF: 0.00 AC: 0 AN: 51630

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.46
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.15	N
REVEL	Benign	0.23
Sift	Benign	0.28	T
Sift4G	Benign	0.51	T
Polyphen		0.61	P
Vest4		0.15
MutPred		0.45		Gain of catalytic residue at A55 (P = 0.0148);
MVP		0.94
MPC		0.64
ClinPred		0.31	T
GERP RS		3.1
Varity_R		0.078
gMVP		0.36
Mutation Taster		=87/13	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: rs772859582; hg19: chr6-19838149;