NM_006383.4:c.87-1999A>G

Variant names:

• chr15-78113275-T-C
• rs16969507
• NM_006383.4:c.87-1999A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006383.4(CIB2):​c.87-1999A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 152,134 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.033 (127 hom., cov: 32)
• Consequence: CIB2 NM_006383.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Usher syndrome type 1J

  Inheritance: Unknown, AR Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive nonsyndromic hearing loss 48

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome type 1

  Inheritance: AR Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006383.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB2	NM_006383.4	MANE Select	c.87-1999A>G		intron	N/A	NP_006374.1
	CIB2	NM_001301224.2		c.87-3766A>G		intron	N/A	NP_001288153.1
	CIB2	NM_001271888.2		c.-43-1999A>G		intron	N/A	NP_001258817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB2	ENST00000258930.8	TSL:1 MANE Select	c.87-1999A>G		intron	N/A	ENSP00000258930.3
	CIB2	ENST00000539011.5	TSL:1	c.-43-1999A>G		intron	N/A	ENSP00000442459.1
	CIB2	ENST00000560618.5	TSL:2	c.-43-1999A>G		intron	N/A	ENSP00000452752.1

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5024 AN: 152014 Hom.: 125 Cov.: 32

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0365

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0204

Gnomad OTH AF: 0.0331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0331 AC: 5038 AN: 152134 Hom.: 127 Cov.: 32 AF XY: 0.0347 AC XY: 2583 AN XY: 74364

African (AFR) AF: 0.0395 AC: 1641 AN: 41508

American (AMR) AF: 0.0366 AC: 560 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.152 AC: 785 AN: 5158

South Asian (SAS) AF: 0.0303 AC: 146 AN: 4818

European-Finnish (FIN) AF: 0.0371 AC: 393 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0204 AC: 1387 AN: 67980

Other (OTH) AF: 0.0342 AC: 72 AN: 2108

Alfa AF: 0.0334 Hom.: 54

Bravo AF: 0.0350

Asia WGS AF: 0.0750 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-0.58
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: rs16969507; hg19: chr15-78405617;