rs77370542

Positions:

chr15-78109278-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006383.4(CIB2):c.303G>A(p.Ser101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 1,609,416 control chromosomes in the GnomAD database, including 1,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 77 hom., cov: 29)

Exomes 𝑓: 0.033 ( 939 hom. )

Consequence

CIB2
NM_006383.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.117

Variant links:

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]

CIB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 15-78109278-C-T is Benign according to our data. Variant chr15-78109278-C-T is described in ClinVar as [Benign]. Clinvar id is 226515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.117 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0239 (3621/151658) while in subpopulation NFE AF= 0.0364 (2470/67894). AF 95% confidence interval is 0.0352. There are 77 homozygotes in gnomad4. There are 1760 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 77 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIB2	NM_006383.4 linkuse as main transcript	c.303G>A	p.Ser101=	synonymous_variant	4/6	ENST00000258930.8	NP_006374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIB2	ENST00000258930.8 linkuse as main transcript	c.303G>A	p.Ser101=	synonymous_variant	4/6	1	NM_006383.4	ENSP00000258930	P1	O75838-1

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3622

AN:

151538

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00672

Gnomad AMI

AF:

0.0562

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.00629

Gnomad FIN

AF:

0.0498

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0241

GnomAD3 exomes

AF:

0.0246

AC:

6189

AN:

251278

Hom.:

114

AF XY:

0.0251

AC XY:

3405

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.00566

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.00630

Gnomad FIN exome

AF:

0.0447

Gnomad NFE exome

AF:

0.0367

Gnomad OTH exome

AF:

0.0269

GnomAD4 exome

AF:

0.0333

AC:

48601

AN:

1457758

Hom.:

939

Cov.:

AF XY:

0.0326

AC XY:

23607

AN XY:

725088

show subpopulations

Gnomad4 AFR exome

AF:

0.00512

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.000711

Gnomad4 SAS exome

AF:

0.00735

Gnomad4 FIN exome

AF:

0.0439

Gnomad4 NFE exome

AF:

0.0386

Gnomad4 OTH exome

AF:

0.0286

GnomAD4 genome

AF:

0.0239

AC:

3621

AN:

151658

Hom.:

Cov.:

AF XY:

0.0238

AC XY:

1760

AN XY:

74082

show subpopulations

Gnomad4 AFR

AF:

0.00670

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000585

Gnomad4 SAS

AF:

0.00630

Gnomad4 FIN

AF:

0.0498

Gnomad4 NFE

AF:

0.0364

Gnomad4 OTH

AF:

0.0238

Alfa

AF:

0.0299

Hom.:

Bravo

AF:

0.0208

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0357

EpiControl

AF:

0.0330

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ser101Ser in exon 4 of CIB2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 3.6% (308/8586) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs77370542). -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 18, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

6.5

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over