15-78105013-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006383.4(CIB2):c.*298C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0072 in 433,930 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (15 hom.)
• Consequence: CIB2 NM_006383.4 3_prime_UTR
• Clinical Significance: Likely 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-C is Benign according to our data. Variant chr15-78105013-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1189907.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00705 (1072/152020) while in subpopulation NFE AF= 0.0117 (798/67932). AF 95% confidence interval is 0.0111. There are 9 homozygotes in gnomad4. There are 458 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00706 AC: 1073 AN: 151902 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.00719

GnomAD4 exome AF: 0.00728 AC: 2053 AN: 281910 Hom.: 15 Cov.: 3 AF XY: 0.00699 AC XY: 1033 AN XY: 147706

Gnomad4 AFR exome AF: 0.00132

Gnomad4 AMR exome AF: 0.00838

Gnomad4 ASJ exome AF: 0.00841

Gnomad4 EAS exome AF: 0.000107

Gnomad4 SAS exome AF: 0.00143

Gnomad4 FIN exome AF: 0.00189

Gnomad4 NFE exome AF: 0.0100

Gnomad4 OTH exome AF: 0.00695

GnomAD4 genome AF: 0.00705 AC: 1072 AN: 152020 Hom.: 9 Cov.: 32 AF XY: 0.00616 AC XY: 458 AN XY: 74296

Gnomad4 AFR AF: 0.00275

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00923

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00377 Hom.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.4
Dann	Benign	0.52
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;