chr15-90230550-C-T

Variant names:

• chr15-90230550-C-T
• rs2073706
• NM_006384.4:c.555-45G>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.555-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,548,520 control chromosomes in the GnomAD database, including 199,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18632 hom., cov: 32)
  • Exomes 𝑓: 0.50 (180377 hom.)
• Consequence: CIB1 NM_006384.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-90230550-C-T is Benign according to our data. Variant chr15-90230550-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688352.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 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.555-45G>A		intron	N/A	NP_006375.2	Q99828-1
	CIB1	NM_001277764.2		c.675-45G>A		intron	N/A	NP_001264693.1	Q99828-2
	CIB1	NR_102427.1		n.741-45G>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.555-45G>A		intron	N/A	ENSP00000333873.6	Q99828-1
	CIB1	ENST00000612800.1	TSL:1	c.675-45G>A		intron	N/A	ENSP00000479860.1	Q99828-2
	CIB1	ENST00000970526.1		c.555-18G>A		intron	N/A	ENSP00000640585.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73946 AN: 151900 Hom.: 18621 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.491

GnomAD2 exomes AF: 0.555 AC: 86289 AN: 155574 AF XY: 0.559

Gnomad AFR exome AF: 0.377

Gnomad AMR exome AF: 0.650

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.824

Gnomad FIN exome AF: 0.539

Gnomad NFE exome AF: 0.476

Gnomad OTH exome AF: 0.520

GnomAD4 exome AF: 0.503 AC: 702442 AN: 1396502 Hom.: 180377 Cov.: 32 AF XY: 0.507 AC XY: 349286 AN XY: 688972

African (AFR) AF: 0.382 AC: 12039 AN: 31540

American (AMR) AF: 0.641 AC: 22895 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 11494 AN: 25154

East Asian (EAS) AF: 0.775 AC: 27671 AN: 35720

South Asian (SAS) AF: 0.638 AC: 50528 AN: 79164

European-Finnish (FIN) AF: 0.535 AC: 26325 AN: 49250

Middle Eastern (MID) AF: 0.472 AC: 2652 AN: 5622

European-Non Finnish (NFE) AF: 0.482 AC: 519369 AN: 1076480

Other (OTH) AF: 0.509 AC: 29469 AN: 57880

GnomAD4 genome AF: 0.487 AC: 73989 AN: 152018 Hom.: 18632 Cov.: 32 AF XY: 0.497 AC XY: 36918 AN XY: 74310

African (AFR) AF: 0.391 AC: 16203 AN: 41452

American (AMR) AF: 0.586 AC: 8961 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1573 AN: 3472

East Asian (EAS) AF: 0.816 AC: 4220 AN: 5174

South Asian (SAS) AF: 0.641 AC: 3085 AN: 4816

European-Finnish (FIN) AF: 0.534 AC: 5645 AN: 10570

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32757 AN: 67926

Other (OTH) AF: 0.494 AC: 1044 AN: 2112

Alfa AF: 0.472 Hom.: 3240

Bravo AF: 0.481

Asia WGS AF: 0.692 AC: 2403 AN: 3478

ClinVar

ClinVar submissions

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	-0.84
CADD	Benign	0.11
DANN	Benign	0.71
PhyloP100		-1.6
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: rs2073706; hg19: chr15-90773782; COSMIC: COSV60173761; COSMIC: COSV60173761;