15-78113275-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIB2	NM_006383.4	c.87-1999A>G		intron_variant	Intron 2 of 5	ENST00000258930.8	NP_006374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIB2	ENST00000258930.8	c.87-1999A>G		intron_variant	Intron 2 of 5	1	NM_006383.4	ENSP00000258930.3

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

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.0366

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0303

Gnomad4 FIN AF: 0.0371

Gnomad4 NFE AF: 0.0204

Gnomad4 OTH AF: 0.0342

Alfa AF: 0.0296 Hom.: 19

Bravo AF: 0.0350

Asia WGS AF: 0.0750 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.50

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: rs16969507; hg19: chr15-78405617;