NM_006383.4:c.542+20C>T

Variant names:

• chr15-78105719-G-A
• rs779956169
• NM_006383.4:c.542+20C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_006383.4(CIB2):​c.542+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CIB2 NM_006383.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00100
• 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 (MetaRNN=0.107827455).
• BP6: Variant 15-78105719-G-A is Benign according to our data. Variant chr15-78105719-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1117369.Status of the report is criteria_provided_single_submitter, 1 stars.

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.542+20C>T		intron	N/A	NP_006374.1	O75838-1
	CIB2	NM_001301224.2		c.557+20C>T		intron	N/A	NP_001288153.1
	CIB2	NM_001271888.2		c.413+20C>T		intron	N/A	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.542+20C>T		intron	N/A	ENSP00000258930.3	O75838-1
	CIB2	ENST00000539011.5	TSL:1	c.413+20C>T		intron	N/A	ENSP00000442459.1	O75838-3
	CIB2	ENST00000560618.5	TSL:2	c.433C>T	p.Arg145Trp	missense	Exon 4 of 4	ENSP00000452752.1	H0YKC8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 250578 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461320 Hom.: 0 Cov.: 34 AF XY: 0.0000248 AC XY: 18 AN XY: 726942

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86258

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111906

Other (OTH) AF: 0.0000331 AC: 2 AN: 60374

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.70
DANN	Benign	0.88
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.11	T
PhyloP100		0.0010
PROVEAN	Benign	0.090	N
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.048	D
Vest4		0.10
MVP		0.85
GERP RS		-6.8
Mutation Taster		=100/0	polymorphism

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: rs779956169; hg19: chr15-78398061;