rs141932061

Variant names:

• chr15-78105833-C-A
• rs141932061
• NM_006383.4:c.448G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78105833-C-A
• chr15-78105833-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006383.4(CIB2):​c.448G>T​(p.Asp150Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D150N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIB2 NM_006383.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.09
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIB2	NM_006383.4	c.448G>T	p.Asp150Tyr	missense_variant	Exon 5 of 6	ENST00000258930.8	NP_006374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIB2	ENST00000258930.8	c.448G>T	p.Asp150Tyr	missense_variant	Exon 5 of 6	1	NM_006383.4	ENSP00000258930.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D;.;.;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Uncertain	2.9	M;.;.;.
PhyloP100		6.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.5	D;D;D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.98	D;.;.;.
Vest4		0.52
MutPred		0.57		Loss of disorder (P = 0.0566);.;.;.;
MVP		0.94
MPC		0.86
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.80
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141932061; hg19: chr15-78398175;