rs7164338

chr15-78105504-T-C

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.543-172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,493,778 control chromosomes in the GnomAD database, including 49,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3871 hom., cov: 32)
  • Exomes 𝑓: 0.26 (45554 hom.)
• Consequence: CIB2 NM_006383.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.771

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=-0.85).
• BP6: Variant 15-78105504-T-C is Benign according to our data. Variant chr15-78105504-T-C is described in ClinVar as [Benign]. Clinvar id is 1245883.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIB2	NM_006383.4	c.543-172A>G		intron_variant		ENST00000258930.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIB2	ENST00000258930.8	c.543-172A>G		intron_variant		1	NM_006383.4	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31981 AN: 151926 Hom.: 3876 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.257 AC: 345243 AN: 1341734 Hom.: 45554 Cov.: 34 AF XY: 0.256 AC XY: 168138 AN XY: 656852

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.210 AC: 31972 AN: 152044 Hom.: 3871 Cov.: 32 AF XY: 0.213 AC XY: 15848 AN XY: 74308

Gnomad4 AFR AF: 0.0869

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.224

Alfa AF: 0.245 Hom.: 792

Bravo AF: 0.196

Asia WGS AF: 0.165 AC: 576 AN: 3478

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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.3
Dann	Benign	0.60

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: rs7164338; hg19: chr15-78397846;