chr1-63521194-T-C

Variant names:

• chr1-63521194-T-C
• rs17391823
• NM_014288.5:c.5+1935A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014288.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3BP	NM_014288.5	MANE Select	c.5+1935A>G		intron	N/A	NP_055103.3
	ITGB3BP	NM_001206739.2		c.5+1935A>G		intron	N/A	NP_001193668.1
	ITGB3BP	NM_001347145.2		c.5+1935A>G		intron	N/A	NP_001334074.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3BP	ENST00000271002.15	TSL:1 MANE Select	c.5+1935A>G		intron	N/A	ENSP00000271002.10
	ITGB3BP	ENST00000371092.7	TSL:1	c.5+1935A>G		intron	N/A	ENSP00000360133.3
	ITGB3BP	ENST00000489099.5	TSL:1	n.5+1935A>G		intron	N/A	ENSP00000432904.1

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

African (AFR) AF: 0.126 AC: 5218 AN: 41344

American (AMR) AF: 0.233 AC: 3559 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3466

East Asian (EAS) AF: 0.141 AC: 727 AN: 5168

South Asian (SAS) AF: 0.136 AC: 654 AN: 4824

European-Finnish (FIN) AF: 0.318 AC: 3341 AN: 10492

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21429 AN: 67906

Other (OTH) AF: 0.233 AC: 490 AN: 2104

Alfa AF: 0.273 Hom.: 1093

Bravo AF: 0.228

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.3
DANN	Benign	0.73
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17391823; hg19: chr1-63986865;