rs17391823

Positions:

• chr1-63521194-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014288.5(ITGB3BP):​c.5+1935A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,764 control chromosomes in the GnomAD database, including 5,014 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 0.24 (5014 hom., cov: 30)
• Consequence: ITGB3BP NM_014288.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB3BP	NM_014288.5	c.5+1935A>G		intron_variant		ENST00000271002.15	NP_055103.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB3BP	ENST00000271002.15	c.5+1935A>G		intron_variant		1	NM_014288.5	ENSP00000271002	P2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36507 AN: 151646 Hom.: 5011 Cov.: 30

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.241 AC: 36517 AN: 151764 Hom.: 5014 Cov.: 30 AF XY: 0.239 AC XY: 17743 AN XY: 74182

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.233

Alfa AF: 0.277 Hom.: 1089

Bravo AF: 0.228

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.3
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs17391823; hg19: chr1-63986865;