1-63327484-A-G

Variant names:

• chr1-63327484-A-G
• rs10749738
• ENST00000771635.1:n.757T>C

Variant summary

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

The ENST00000771635.1(ENSG00000300433):​n.757T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,128 control chromosomes in the GnomAD database, including 37,173 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 0.70 (37173 hom., cov: 33)
• Consequence: ENSG00000300433 ENST00000771635.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 4 publications found

Genes affected

ENSG00000300433 (HGNC:):

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000771635.1. 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
	ENSG00000300433	ENST00000771635.1		n.757T>C		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000300433	ENST00000771636.1		n.761T>C		non_coding_transcript_exon	Exon 2 of 2
	ITGB3BP	ENST00000717656.1		n.340-6021T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106122 AN: 152010 Hom.: 37133 Cov.: 33

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.698 AC: 106219 AN: 152128 Hom.: 37173 Cov.: 33 AF XY: 0.694 AC XY: 51639 AN XY: 74368

African (AFR) AF: 0.740 AC: 30719 AN: 41512

American (AMR) AF: 0.637 AC: 9742 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2546 AN: 3470

East Asian (EAS) AF: 0.663 AC: 3422 AN: 5158

South Asian (SAS) AF: 0.736 AC: 3545 AN: 4818

European-Finnish (FIN) AF: 0.663 AC: 7015 AN: 10574

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46876 AN: 67982

Other (OTH) AF: 0.701 AC: 1483 AN: 2116

Alfa AF: 0.694 Hom.: 61862

Bravo AF: 0.697

Asia WGS AF: 0.719 AC: 2504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.79
PhyloP100		0.052

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10749738;

hg19: chr1-63793155;

COSMIC: COSV64379837;