Variant chr14-99851135-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+100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,256,282 control chromosomes in the GnomAD database, including 49,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4637 hom., cov: 31)

Exomes 𝑓: 0.28 ( 45222 hom. )

Consequence

EML1
NM_004434.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.377

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=-0.68).

BP6

Variant 14-99851135-G-A is Benign according to our data. Variant chr14-99851135-G-A is described in ClinVar as [Benign]. Clinvar id is 1270654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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+100G>A		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+100G>A		intron_variant		1	NM_004434.3	P1	O00423-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34210

AN:

151914

Hom.:

4633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0948

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.228

GnomAD4 exome

AF:

0.279

AC:

307807

AN:

1104250

Hom.:

45222

AF XY:

0.275

AC XY:

150091

AN XY:

545026

show subpopulations

Gnomad4 AFR exome

AF:

0.0849

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.127

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.361

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.225

AC:

34215

AN:

152032

Hom.:

4637

Cov.:

AF XY:

0.224

AC XY:

16654

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0946

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.284

Hom.:

8378

Bravo

AF:

0.208

Asia WGS

AF:

0.177

AC:

617

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.2

DANN

Benign

0.89

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