Variant chr14-99865539-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004434.3(EML1):c.276T>C(p.Pro92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,898 control chromosomes in the GnomAD database, including 75,902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5842 hom., cov: 32)

Exomes 𝑓: 0.30 ( 70060 hom. )

Consequence

EML1
NM_004434.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.405

Variant links:

Genes affected

EML1 (HGNC:3330): (EMAP like 1) Human echinoderm microtubule-associated protein-like is a strong candidate for the Usher syndrome type 1A gene. Usher syndromes (USHs) are a group of genetic disorders consisting of congenital deafness, retinitis pigmentosa, and vestibular dysfunction of variable onset and severity depending on the genetic type. The disease process in USHs involves the entire brain and is not limited to the posterior fossa or auditory and visual systems. The USHs are catagorized as type I (USH1A, USH1B, USH1C, USH1D, USH1E and USH1F), type II (USH2A and USH2B) and type III (USH3). The type I is the most severe form. Gene loci responsible for these three types are all mapped. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

EML1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 14-99865539-T-C is Benign according to our data. Variant chr14-99865539-T-C is described in ClinVar as [Benign]. Clinvar id is 1255382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-99865539-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.405 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML1	NM_004434.3 linkuse as main transcript	c.276T>C	p.Pro92=	synonymous_variant	3/22	ENST00000262233.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML1	ENST00000262233.11 linkuse as main transcript	c.276T>C	p.Pro92=	synonymous_variant	3/22	1	NM_004434.3	P1	O00423-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40373

AN:

152034

Hom.:

5836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.268

AC:

67350

AN:

251360

Hom.:

10064

AF XY:

0.270

AC XY:

36633

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.303

AC:

443524

AN:

1461746

Hom.:

70060

Cov.:

AF XY:

0.300

AC XY:

218219

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.284

GnomAD4 genome

AF:

0.266

AC:

40397

AN:

152152

Hom.:

5842

Cov.:

AF XY:

0.264

AC XY:

19638

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.305

Hom.:

11505

Bravo

AF:

0.251

Asia WGS

AF:

0.196

AC:

680

AN:

3478

EpiCase

AF:

0.312

EpiControl

AF:

0.314

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Band heterotopia of brain

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.6

DANN

Benign

0.81

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over