15-78105013-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006383.4(CIB2):c.*298C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 433,530 control chromosomes in the GnomAD database, including 2,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (700 hom., cov: 32)
  • Exomes 𝑓: 0.098 (1609 hom.)
• Consequence: CIB2 NM_006383.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.22

Genes affected

CIB2 (HGNC:24579): (calcium and integrin binding family member 2) The protein encoded by this gene is similar to that of KIP/CIB, calcineurin B, and calmodulin. The encoded protein is a calcium-binding regulatory protein that interacts with DNA-dependent protein kinase catalytic subunits (DNA-PKcs), and it is involved in photoreceptor cell maintenance. Mutations in this gene cause deafness, autosomal recessive, 48 (DFNB48), and also Usher syndrome 1J (USH1J). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-78105013-G-T is Benign according to our data. Variant chr15-78105013-G-T is described in ClinVar as [Benign]. Clinvar id is 1287164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIB2	NM_006383.4	c.*298C>A		3_prime_UTR_variant	6/6	ENST00000258930.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIB2	ENST00000258930.8	c.*298C>A		3_prime_UTR_variant	6/6	1	NM_006383.4	P1
CIB2	ENST00000539011.5	c.*298C>A		3_prime_UTR_variant	5/5	1
CIB2	ENST00000557846.5	c.*298C>A		3_prime_UTR_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 13614 AN: 151862 Hom.: 700 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0635

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0675

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0979 AC: 27562 AN: 281550 Hom.: 1609 Cov.: 3 AF XY: 0.0951 AC XY: 14037 AN XY: 147526

Gnomad4 AFR exome AF: 0.0265

Gnomad4 AMR exome AF: 0.0769

Gnomad4 ASJ exome AF: 0.0616

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0538

Gnomad4 FIN exome AF: 0.0992

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.0991

GnomAD4 genome AF: 0.0896 AC: 13615 AN: 151980 Hom.: 700 Cov.: 32 AF XY: 0.0900 AC XY: 6681 AN XY: 74272

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.0892

Gnomad4 ASJ AF: 0.0635

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0676

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0251 Hom.: 31

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.7
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs112196879; hg19: chr15-78397355;