Variant chr14-99851039-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004434.3(EML1):c.250+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,604,730 control chromosomes in the GnomAD database, including 66,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4644 hom., cov: 31)

Exomes 𝑓: 0.28 ( 61573 hom. )

Consequence

EML1
NM_004434.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.0003956

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.70

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-99851039-G-A is Benign according to our data. Variant chr14-99851039-G-A is described in ClinVar as [Benign]. Clinvar id is 1286842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-99851039-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 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.250+4G>A		splice_donor_region_variant, intron_variant		ENST00000262233.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML1	ENST00000262233.11 linkuse as main transcript	c.250+4G>A		splice_donor_region_variant, intron_variant		1	NM_004434.3	P1	O00423-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34228

AN:

152000

Hom.:

4640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0946

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.226

GnomAD3 exomes

AF:

0.245

AC:

61058

AN:

249392

Hom.:

8453

AF XY:

0.247

AC XY:

33325

AN XY:

134714

show subpopulations

Gnomad AFR exome

AF:

0.0918

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.284

AC:

412355

AN:

1452612

Hom.:

61573

Cov.:

AF XY:

0.281

AC XY:

202190

AN XY:

720762

show subpopulations

Gnomad4 AFR exome

AF:

0.0863

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.287

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.366

Gnomad4 NFE exome

AF:

0.307

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.225

AC:

34233

AN:

152118

Hom.:

4644

Cov.:

AF XY:

0.224

AC XY:

16665

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0944

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.256

Hom.:

1675

Bravo

AF:

0.208

Asia WGS

AF:

0.177

AC:

615

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00040

dbscSNV1_RF

Benign

0.046

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