20-31605597-C-G

Variant names:

• chr20-31605597-C-G
• rs975434088
• NM_002165.4:c.210C>G

Variant summary

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

The NM_002165.4(ID1):​c.210C>G​(p.Asn70Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,772 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N70N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ID1 NM_002165.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• Publications: 0 publications found

Genes affected

ID1 (HGNC:5360): (inhibitor of DNA binding 1) The protein encoded by this gene is a helix-loop-helix (HLH) protein that can form heterodimers with members of the basic HLH family of transcription factors. The encoded protein has no DNA binding activity and therefore can inhibit the DNA binding and transcriptional activation ability of basic HLH proteins with which it interacts. This protein may play a role in cell growth, senescence, and differentiation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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_002165.4. 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
	ID1	NM_002165.4	MANE Select	c.210C>G	p.Asn70Lys	missense	Exon 1 of 2	NP_002156.2
	ID1	NM_181353.3		c.210C>G	p.Asn70Lys	missense	Exon 1 of 1	NP_851998.1	P41134-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ID1	ENST00000376112.4	TSL:1 MANE Select	c.210C>G	p.Asn70Lys	missense	Exon 1 of 2	ENSP00000365280.3	P41134-1
	ID1	ENST00000718307.1		c.210C>G	p.Asn70Lys	missense	Exon 4 of 5	ENSP00000520744.1	P41134-1
	ID1	ENST00000718308.1		c.210C>G	p.Asn70Lys	missense	Exon 2 of 3	ENSP00000520745.1	P41134-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000551 AC: 1 AN: 181648 AF XY: 0.0000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000377

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: 7.05e-7 AC: 1 AN: 1417772 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 701532

African (AFR) AF: 0.00 AC: 0 AN: 32178

American (AMR) AF: 0.0000267 AC: 1 AN: 37408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25356

East Asian (EAS) AF: 0.00 AC: 0 AN: 36708

South Asian (SAS) AF: 0.00 AC: 0 AN: 81302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089928

Other (OTH) AF: 0.00 AC: 0 AN: 58804

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.96	D
Eigen	Benign	0.069
Eigen_PC	Benign	0.015
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.39	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.31
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.63
Sift	Benign	0.086	T
Sift4G	Uncertain	0.052	T
Polyphen		0.60	P
Vest4		0.35
MutPred		0.78		Gain of ubiquitination at N70 (P = 0.0311)
MVP		0.99
MPC		0.19
ClinPred		0.84	D
GERP RS		3.9
PromoterAI		0.011	Neutral
Varity_R		0.59
gMVP		0.80
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs975434088; hg19: chr20-30193400;