1-63576116-C-T

Position:

• chr1-63576116-C-T

Variant summary

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

The XM_011542301.3(EFCAB7):​c.1854+4988C>T 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: EFCAB7 XM_011542301.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

Genes affected

EFCAB7 (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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCAB7	XM_011542301.3	c.1854+4988C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB3BP	ENST00000478138.1	n.197+17409G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.607

Alfa AF: 0.527 Hom.: 9911

Bravo AF: 0.630

Asia WGS AF: 0.656 AC: 2284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs217463; hg19: chr1-64041787;