rs11633444

Variant names:

• chr15-78105126-G-A
• rs11633444
• NM_006383.4:c.*185C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78105126-G-A
• chr15-78105126-G-C
• chr15-78105126-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006383.4(CIB2):​c.*185C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 620,364 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CIB2 NM_006383.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• 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
• hearing loss, autosomal recessive

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB2	NM_006383.4	MANE Select	c.*185C>T		3_prime_UTR	Exon 6 of 6	NP_006374.1	O75838-1
	CIB2	NM_001301224.2		c.*185C>T		3_prime_UTR	Exon 5 of 5	NP_001288153.1
	CIB2	NM_001271888.2		c.*185C>T		3_prime_UTR	Exon 5 of 5	NP_001258817.1	O75838-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB2	ENST00000258930.8	TSL:1 MANE Select	c.*185C>T		3_prime_UTR	Exon 6 of 6	ENSP00000258930.3	O75838-1
	CIB2	ENST00000539011.5	TSL:1	c.*185C>T		3_prime_UTR	Exon 5 of 5	ENSP00000442459.1	O75838-3
	CIB2	ENST00000958911.1		c.*185C>T		3_prime_UTR	Exon 6 of 6	ENSP00000628970.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000161 AC: 1 AN: 620364 Hom.: 0 Cov.: 8 AF XY: 0.00000313 AC XY: 1 AN XY: 319878

African (AFR) AF: 0.00 AC: 0 AN: 15404

American (AMR) AF: 0.00 AC: 0 AN: 20380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14560

East Asian (EAS) AF: 0.00 AC: 0 AN: 30488

South Asian (SAS) AF: 0.00 AC: 0 AN: 50160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2448

European-Non Finnish (NFE) AF: 0.00000235 AC: 1 AN: 425330

Other (OTH) AF: 0.00 AC: 0 AN: 30756

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11633444; hg19: chr15-78397468;