15-90230807-C-T

Variant names:

• chr15-90230807-C-T
• rs2073705
• NM_006384.4:c.554+127G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006384.4(CIB1):​c.554+127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 887,354 control chromosomes in the GnomAD database, including 41,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (6195 hom., cov: 33)
  • Exomes 𝑓: 0.28 (35693 hom.)
• Consequence: CIB1 NM_006384.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.754
• Publications: 3 publications found

Genes affected

CIB1 (HGNC:16920): (calcium and integrin binding 1) This gene encodes a member of the EF-hand domain-containing calcium-binding superfamily. The encoded protein interacts with many other proteins, including the platelet integrin alpha-IIb-beta-3, DNA-dependent protein kinase, presenilin-2, focal adhesion kinase, p21 activated kinase, and protein kinase D. The encoded protein may be involved in cell survival and proliferation, and is associated with several disease states including cancer and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

CIB1 Gene-Disease associations (from GenCC):

• epidermodysplasia verruciformis, susceptibility to, 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• epidermodysplasia verruciformis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-90230807-C-T is Benign according to our data. Variant chr15-90230807-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006384.4. 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
	CIB1	NM_006384.4	MANE Select	c.554+127G>A		intron	N/A	NP_006375.2	Q99828-1
	CIB1	NM_001277764.2		c.674+127G>A		intron	N/A	NP_001264693.1	Q99828-2
	CIB1	NR_102427.1		n.740+127G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB1	ENST00000328649.11	TSL:1 MANE Select	c.554+127G>A		intron	N/A	ENSP00000333873.6	Q99828-1
	CIB1	ENST00000612800.1	TSL:1	c.674+127G>A		intron	N/A	ENSP00000479860.1	Q99828-2
	CIB1	ENST00000970526.1		c.554+127G>A		intron	N/A	ENSP00000640585.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40103 AN: 151982 Hom.: 6186 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.284 AC: 209135 AN: 735252 Hom.: 35693 AF XY: 0.288 AC XY: 111893 AN XY: 387986

African (AFR) AF: 0.191 AC: 3761 AN: 19646

American (AMR) AF: 0.506 AC: 19970 AN: 39466

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 3595 AN: 19374

East Asian (EAS) AF: 0.661 AC: 23822 AN: 36038

South Asian (SAS) AF: 0.416 AC: 27812 AN: 66882

European-Finnish (FIN) AF: 0.273 AC: 12331 AN: 45206

Middle Eastern (MID) AF: 0.220 AC: 586 AN: 2660

European-Non Finnish (NFE) AF: 0.229 AC: 107531 AN: 469860

Other (OTH) AF: 0.269 AC: 9727 AN: 36120

GnomAD4 genome AF: 0.264 AC: 40130 AN: 152102 Hom.: 6195 Cov.: 33 AF XY: 0.274 AC XY: 20403 AN XY: 74346

African (AFR) AF: 0.200 AC: 8301 AN: 41486

American (AMR) AF: 0.399 AC: 6105 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3470

East Asian (EAS) AF: 0.695 AC: 3592 AN: 5166

South Asian (SAS) AF: 0.423 AC: 2040 AN: 4826

European-Finnish (FIN) AF: 0.269 AC: 2844 AN: 10584

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15883 AN: 67972

Other (OTH) AF: 0.272 AC: 572 AN: 2106

Alfa AF: 0.238 Hom.: 750

Bravo AF: 0.269

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.55
PhyloP100		-0.75
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: rs2073705; hg19: chr15-90774039;