14-30890641-T-G

Variant names:

• chr14-30890641-T-G
• rs6571366
• ENST00000475087.5:c.1478-4272T>G

Variant summary

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

The ENST00000475087.5(COCH):​c.1478-4272T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COCH ENST00000475087.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821
• Publications: 2 publications found

Genes affected

COCH (HGNC:2180): (cochlin) The protein encoded by this gene is highly conserved in human, mouse, and chicken, showing 94% and 79% amino acid identity of human to mouse and chicken sequences, respectively. Hybridization to this gene was detected in spindle-shaped cells located along nerve fibers between the auditory ganglion and sensory epithelium. These cells accompany neurites at the habenula perforata, the opening through which neurites extend to innervate hair cells. This and the pattern of expression of this gene in chicken inner ear paralleled the histologic findings of acidophilic deposits, consistent with mucopolysaccharide ground substance, in temporal bones from DFNA9 (autosomal dominant nonsyndromic sensorineural deafness 9) patients. Mutations that cause DFNA9 have been reported in this gene. Alternative splicing results in multiple transcript variants encoding the same protein. Additional splice variants encoding distinct isoforms have been described but their biological validities have not been demonstrated. [provided by RefSeq, Oct 2008]

COCH Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive 110

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000475087.5. 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
	COCH	NM_004086.3	MANE Select	c.*850T>G		downstream_gene	N/A	NP_004077.1	O43405-1
	COCH	NM_001347720.2		c.*850T>G		downstream_gene	N/A	NP_001334649.1	A0A2U3TZE7
	COCH	NM_001135058.2		c.*850T>G		downstream_gene	N/A	NP_001128530.1	O43405-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COCH	ENST00000475087.5	TSL:1	c.1478-4272T>G		intron	N/A	ENSP00000451528.1	O43405-2
	COCH	ENST00000643575.1		c.*2+848T>G		intron	N/A	ENSP00000494838.1	O43405-1
	COCH	ENST00000964788.1		c.*2+848T>G		intron	N/A	ENSP00000634847.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 754736 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 350844

African (AFR) AF: 0.00 AC: 0 AN: 14076

American (AMR) AF: 0.00 AC: 0 AN: 880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4666

East Asian (EAS) AF: 0.00 AC: 0 AN: 3178

South Asian (SAS) AF: 0.00 AC: 0 AN: 14826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 690382

Other (OTH) AF: 0.00 AC: 0 AN: 24568

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 4076

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.32
DANN	Benign	0.14
PhyloP100		-0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6571366; hg19: chr14-31359847;