Variant 14-99850935-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_004434.3(EML1):c.150C>T(p.Asp50=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 1,614,112 control chromosomes in the GnomAD database, including 440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 34 hom., cov: 31)

Exomes 𝑓: 0.021 ( 406 hom. )

Consequence

EML1
NM_004434.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.493

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 14-99850935-C-T is Benign according to our data. Variant chr14-99850935-C-T is described in ClinVar as [Benign]. Clinvar id is 1579199.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-99850935-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.493 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0164 (2499/152238) while in subpopulation NFE AF= 0.0246 (1674/68014). AF 95% confidence interval is 0.0236. There are 34 homozygotes in gnomad4. There are 1235 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML1	NM_004434.3 linkuse as main transcript	c.150C>T	p.Asp50=	synonymous_variant	2/22	ENST00000262233.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML1	ENST00000262233.11 linkuse as main transcript	c.150C>T	p.Asp50=	synonymous_variant	2/22	1	NM_004434.3	P1	O00423-1

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2499

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00353

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.0385

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0165

AC:

4142

AN:

251482

Hom.:

AF XY:

0.0164

AC XY:

2234

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.00512

Gnomad ASJ exome

AF:

0.0192

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00670

Gnomad FIN exome

AF:

0.0362

Gnomad NFE exome

AF:

0.0230

Gnomad OTH exome

AF:

0.0168

GnomAD4 exome

AF:

0.0210

AC:

30644

AN:

1461874

Hom.:

406

Cov.:

AF XY:

0.0206

AC XY:

14999

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00323

Gnomad4 AMR exome

AF:

0.00563

Gnomad4 ASJ exome

AF:

0.0173

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00634

Gnomad4 FIN exome

AF:

0.0370

Gnomad4 NFE exome

AF:

0.0236

Gnomad4 OTH exome

AF:

0.0176

GnomAD4 genome

AF:

0.0164

AC:

2499

AN:

152238

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1235

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00352

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.0385

Gnomad4 NFE

AF:

0.0246

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0219

Hom.:

Bravo

AF:

0.0135

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0221

EpiControl

AF:

0.0205

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

2.9

DANN

Benign

0.75

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