chr14-30877274-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004086.3(COCH):​c.83-298G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 373,848 control chromosomes in the GnomAD database, including 559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 165 hom., cov: 32)
Exomes 𝑓: 0.054 ( 394 hom. )

Consequence

COCH
NM_004086.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.62
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BP6
Variant 14-30877274-G-A is Benign according to our data. Variant chr14-30877274-G-A is described in ClinVar as [Benign]. Clinvar id is 1221585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COCHNM_004086.3 linkuse as main transcriptc.83-298G>A intron_variant ENST00000396618.9
LOC100506071NR_038356.1 linkuse as main transcriptn.1618-722C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COCHENST00000396618.9 linkuse as main transcriptc.83-298G>A intron_variant 1 NM_004086.3 P1O43405-1
ENST00000555108.1 linkuse as main transcriptn.1618-722C>T intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0383
AC:
5822
AN:
152042
Hom.:
165
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00998
Gnomad AMI
AF:
0.0329
Gnomad AMR
AF:
0.0298
Gnomad ASJ
AF:
0.0476
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0674
Gnomad FIN
AF:
0.0262
Gnomad MID
AF:
0.0570
Gnomad NFE
AF:
0.0597
Gnomad OTH
AF:
0.0379
GnomAD4 exome
AF:
0.0536
AC:
11877
AN:
221690
Hom.:
394
AF XY:
0.0557
AC XY:
6644
AN XY:
119340
show subpopulations
Gnomad4 AFR exome
AF:
0.00964
Gnomad4 AMR exome
AF:
0.0253
Gnomad4 ASJ exome
AF:
0.0437
Gnomad4 EAS exome
AF:
0.0000932
Gnomad4 SAS exome
AF:
0.0716
Gnomad4 FIN exome
AF:
0.0295
Gnomad4 NFE exome
AF:
0.0601
Gnomad4 OTH exome
AF:
0.0491
GnomAD4 genome
AF:
0.0382
AC:
5820
AN:
152158
Hom.:
165
Cov.:
32
AF XY:
0.0372
AC XY:
2768
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.00995
Gnomad4 AMR
AF:
0.0298
Gnomad4 ASJ
AF:
0.0476
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0677
Gnomad4 FIN
AF:
0.0262
Gnomad4 NFE
AF:
0.0597
Gnomad4 OTH
AF:
0.0375
Alfa
AF:
0.0209
Hom.:
14
Bravo
AF:
0.0369
Asia WGS
AF:
0.0210
AC:
74
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxDec 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
1.8
DANN
Benign
0.74

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs77298564; hg19: chr14-31346480; API