rs1044813

Variant names:

• chr15-90231027-G-C
• rs1044813
• NM_006384.4:c.466-5C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-90231027-G-C
• chr15-90231027-G-T
• chr15-90231027-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006384.4(CIB1):​c.466-5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,294 control chromosomes in the GnomAD database, including 66,588 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6162 hom., cov: 32)
  • Exomes 𝑓: 0.27 (60426 hom.)
• Consequence: CIB1 NM_006384.4 splice_region, intron
• Scores: Splicing: ADA: 0.002671
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.323
• Publications: 9 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• epidermodysplasia verruciformis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 15-90231027-G-C is Benign according to our data. Variant chr15-90231027-G-C is described in ClinVar as Benign. ClinVar VariationId is 1167687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 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.466-5C>G		splice_region intron	N/A	NP_006375.2	Q99828-1
	CIB1	NM_001277764.2		c.586-5C>G		splice_region intron	N/A	NP_001264693.1	Q99828-2
	CIB1	NR_102427.1		n.652-5C>G		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB1	ENST00000328649.11	TSL:1 MANE Select	c.466-5C>G		splice_region intron	N/A	ENSP00000333873.6	Q99828-1
	CIB1	ENST00000612800.1	TSL:1	c.586-5C>G		splice_region intron	N/A	ENSP00000479860.1	Q99828-2
	CIB1	ENST00000970526.1		c.466-5C>G		splice_region intron	N/A	ENSP00000640585.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39822 AN: 152036 Hom.: 6154 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.274

GnomAD2 exomes AF: 0.336 AC: 84388 AN: 251272 AF XY: 0.332

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.525

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.707

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.236

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.269 AC: 392589 AN: 1461140 Hom.: 60426 Cov.: 34 AF XY: 0.273 AC XY: 198261 AN XY: 726904

African (AFR) AF: 0.181 AC: 6043 AN: 33462

American (AMR) AF: 0.510 AC: 22819 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4992 AN: 26132

East Asian (EAS) AF: 0.666 AC: 26439 AN: 39698

South Asian (SAS) AF: 0.439 AC: 37881 AN: 86228

European-Finnish (FIN) AF: 0.277 AC: 14771 AN: 53388

Middle Eastern (MID) AF: 0.240 AC: 1385 AN: 5764

European-Non Finnish (NFE) AF: 0.236 AC: 261747 AN: 1111390

Other (OTH) AF: 0.274 AC: 16512 AN: 60354

GnomAD4 genome AF: 0.262 AC: 39844 AN: 152154 Hom.: 6162 Cov.: 32 AF XY: 0.273 AC XY: 20332 AN XY: 74386

African (AFR) AF: 0.188 AC: 7798 AN: 41526

American (AMR) AF: 0.399 AC: 6098 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 626 AN: 3472

East Asian (EAS) AF: 0.694 AC: 3571 AN: 5146

South Asian (SAS) AF: 0.449 AC: 2169 AN: 4830

European-Finnish (FIN) AF: 0.272 AC: 2883 AN: 10598

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15928 AN: 67982

Other (OTH) AF: 0.273 AC: 577 AN: 2112

Alfa AF: 0.234 Hom.: 1433

Bravo AF: 0.266

Asia WGS AF: 0.515 AC: 1789 AN: 3478

EpiCase AF: 0.224

EpiControl AF: 0.228

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CIB1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.6
DANN	Benign	0.81
PhyloP100		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0027
dbscSNV1_RF	Benign	0.054
SpliceAI score (max)		0.020		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: rs1044813; hg19: chr15-90774259; COSMIC: COSV60173766; COSMIC: COSV60173766;