ENST00000478138.1:n.197+2785G>T

Variant names:

• chr1-63590740-C-A
• rs11208250
• ENST00000478138.1:n.197+2785G>T

Variant summary

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

The ENST00000478138.1(ITGB3BP):​n.197+2785G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,946 control chromosomes in the GnomAD database, including 2,208 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2208 hom., cov: 31)
• Consequence: ITGB3BP ENST00000478138.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 2 publications found

Genes affected

ITGB3BP (HGNC:6157): (integrin subunit beta 3 binding protein) This gene encodes a transcriptional coregulator that binds to and enhances the activity of members of the nuclear receptor families, thyroid hormone receptors and retinoid X receptors. This protein also acts as a corepressor of NF-kappaB-dependent signaling. This protein induces apoptosis in breast cancer cells through a caspase 2-mediated signaling pathway. This protein is also a component of the centromere-specific histone H3 variant nucleosome associated complex (CENP-NAC) and may be involved in mitotic progression by recruiting the histone H3 variant CENP-A to the centromere. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3BP	ENST00000478138.1	n.197+2785G>T		intron_variant	Intron 1 of 4	3
ITGB3BP	ENST00000717656.1	n.104+2785G>T		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22742 AN: 151828 Hom.: 2206 Cov.: 31

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.150 AC: 22744 AN: 151946 Hom.: 2208 Cov.: 31 AF XY: 0.153 AC XY: 11329 AN XY: 74240

African (AFR) AF: 0.0398 AC: 1651 AN: 41504

American (AMR) AF: 0.113 AC: 1733 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3470

East Asian (EAS) AF: 0.166 AC: 851 AN: 5124

South Asian (SAS) AF: 0.219 AC: 1050 AN: 4798

European-Finnish (FIN) AF: 0.247 AC: 2602 AN: 10526

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13651 AN: 67936

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.176 Hom.: 6980

Bravo AF: 0.135

Asia WGS AF: 0.189 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.64
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11208250; hg19: chr1-64056411;