1-23559007-T-C

Variant names:

• chr1-23559007-T-C
• rs11574
• NM_002167.5:c.313A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002167.5(ID3):​c.313A>G​(p.Thr105Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,613,428 control chromosomes in the GnomAD database, including 490,712 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (52052 hom., cov: 32)
  • Exomes 𝑓: 0.77 (438660 hom.)
• Consequence: ID3 NM_002167.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• Publications: 66 publications found

Genes affected

ID3 (HGNC:5362): (inhibitor of DNA binding 3) The protein encoded by this gene is a helix-loop-helix (HLH) protein that can form heterodimers with other HLH proteins. However, the encoded protein lacks a basic DNA-binding domain and therefore inhibits the DNA binding of any HLH protein with which it interacts. [provided by RefSeq, Aug 2011]

ENSG00000307540 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.3288456E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ID3	NM_002167.5	c.313A>G	p.Thr105Ala	missense_variant	Exon 2 of 3	ENST00000374561.6	NP_002158.3
LOC124903876	XR_007065537.1	n.282+6912T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ID3	ENST00000374561.6	c.313A>G	p.Thr105Ala	missense_variant	Exon 2 of 3	1	NM_002167.5	ENSP00000363689.5
ID3	ENST00000486541.1	n.330A>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
ID3	ENST00000463312.1	n.69A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
ENSG00000307540	ENST00000826972.1	n.204-13740T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124841 AN: 152080 Hom.: 52002 Cov.: 32

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.842

GnomAD2 exomes AF: 0.797 AC: 200261 AN: 251182 AF XY: 0.804

Gnomad AFR exome AF: 0.953

Gnomad AMR exome AF: 0.702

Gnomad ASJ exome AF: 0.901

Gnomad EAS exome AF: 0.976

Gnomad FIN exome AF: 0.687

Gnomad NFE exome AF: 0.757

Gnomad OTH exome AF: 0.800

GnomAD4 exome AF: 0.771 AC: 1127034 AN: 1461230 Hom.: 438660 Cov.: 51 AF XY: 0.777 AC XY: 564505 AN XY: 726932

African (AFR) AF: 0.957 AC: 32042 AN: 33474

American (AMR) AF: 0.706 AC: 31573 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 23499 AN: 26134

East Asian (EAS) AF: 0.979 AC: 38856 AN: 39698

South Asian (SAS) AF: 0.906 AC: 78127 AN: 86248

European-Finnish (FIN) AF: 0.688 AC: 36764 AN: 53404

Middle Eastern (MID) AF: 0.931 AC: 5368 AN: 5768

European-Non Finnish (NFE) AF: 0.749 AC: 832290 AN: 1111436

Other (OTH) AF: 0.804 AC: 48515 AN: 60370

GnomAD4 genome AF: 0.821 AC: 124953 AN: 152198 Hom.: 52052 Cov.: 32 AF XY: 0.819 AC XY: 60978 AN XY: 74418

African (AFR) AF: 0.949 AC: 39435 AN: 41548

American (AMR) AF: 0.766 AC: 11710 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3147 AN: 3472

East Asian (EAS) AF: 0.974 AC: 5025 AN: 5160

South Asian (SAS) AF: 0.911 AC: 4397 AN: 4826

European-Finnish (FIN) AF: 0.688 AC: 7292 AN: 10602

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51155 AN: 67988

Other (OTH) AF: 0.841 AC: 1776 AN: 2112

Alfa AF: 0.789 Hom.: 114951

Bravo AF: 0.832

TwinsUK AF: 0.755 AC: 2801

ALSPAC AF: 0.749 AC: 2887

ESP6500AA AF: 0.940 AC: 4141

ESP6500EA AF: 0.762 AC: 6549

ExAC AF: 0.803 AC: 97506

Asia WGS AF: 0.930 AC: 3234 AN: 3478

EpiCase AF: 0.784

EpiControl AF: 0.787

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.14
DANN	Benign	0.53
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0086	N
MetaRNN	Benign	6.3e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-0.50
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.044
Sift	Benign	0.86	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.023
MPC		0.12
ClinPred		0.0063	T
GERP RS		-2.8
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.26
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs11574; hg19: chr1-23885498; COSMIC: COSV107485314;