1-63576116-C-T

Variant names:

• chr1-63576116-C-T
• rs217463
• XM_011542301.3:c.1854+4988C>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+17409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,996 control chromosomes in the GnomAD database, including 29,473 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 0.60 (29473 hom., cov: 31)
• Consequence: ITGB3BP ENST00000478138.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 10 publications found

Genes affected

EFCAB7 (HGNC:29379): (EF-hand calcium binding domain 7) Predicted to enable calcium ion binding activity. Predicted to be involved in positive regulation of protein import into nucleus; positive regulation of protein localization to ciliary membrane; and positive regulation of transcription by RNA polymerase II. Predicted to be located in ciliary membrane. Predicted to be extrinsic component of membrane. Predicted to be part of plasma membrane protein complex. [provided by Alliance of Genome Resources, Apr 2022]

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]

ENSG00000300414 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000478138.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3BP	ENST00000478138.1	TSL:3	n.197+17409G>A		intron	N/A
	ITGB3BP	ENST00000717656.1		n.104+17409G>A		intron	N/A
	ENSG00000300414	ENST00000771503.1		n.169+2000C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91699 AN: 151876 Hom.: 29426 Cov.: 31

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.604 AC: 91798 AN: 151996 Hom.: 29473 Cov.: 31 AF XY: 0.602 AC XY: 44763 AN XY: 74300

African (AFR) AF: 0.819 AC: 33972 AN: 41480

American (AMR) AF: 0.650 AC: 9926 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2058 AN: 3468

East Asian (EAS) AF: 0.676 AC: 3496 AN: 5168

South Asian (SAS) AF: 0.639 AC: 3077 AN: 4812

European-Finnish (FIN) AF: 0.433 AC: 4569 AN: 10544

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32798 AN: 67948

Other (OTH) AF: 0.607 AC: 1277 AN: 2104

Alfa AF: 0.538 Hom.: 15229

Bravo AF: 0.630

Asia WGS AF: 0.656 AC: 2284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.59
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs217463; hg19: chr1-64041787;