Genetic Variant EML1:c.28+9112G>A (chr14-99746972-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000554479.5(EML1):c.28+9112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,752 control chromosomes in the GnomAD database, including 23,224 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 23224 hom., cov: 30)

Consequence

EML1
ENST00000554479.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.170

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

band heterotopia of brain
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
subcortical band heterotopia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EML1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
EML1	NM_001375411.1 link	c.28+9112G>A	intron_variant	Intron 1 of 21	NP_001362340.1
EML1	NM_001440377.1 link	c.28+9112G>A	intron_variant	Intron 1 of 20	NP_001427306.1
EML1	XM_005267398.3 link	c.28+9112G>A	intron_variant	Intron 1 of 22	XP_005267455.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML1	ENST00000554479.5 link	c.28+9112G>A		intron_variant	Intron 1 of 10	1		ENSP00000451346.1		G3V3N9
EML1	ENST00000555145.5 link	c.28+9112G>A		intron_variant	Intron 1 of 4	4		ENSP00000452160.1		G3V538

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78850

AN:

151634

Hom.:

23208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.604

Gnomad ASJ

AF:

0.636

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.707

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.520

AC:

78893

AN:

151752

Hom.:

23224

Cov.:

AF XY:

0.525

AC XY:

38942

AN XY:

74124

show subpopulations

African (AFR)

AF:

0.221

AC:

9136

AN:

41426

American (AMR)

AF:

0.604

AC:

9208

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

2206

AN:

3466

East Asian (EAS)

AF:

0.535

AC:

2740

AN:

5120

South Asian (SAS)

AF:

0.578

AC:

2773

AN:

4798

European-Finnish (FIN)

AF:

0.707

AC:

7432

AN:

10518

Middle Eastern (MID)

AF:

0.680

AC:

200

AN:

294

European-Non Finnish (NFE)

AF:

0.640

AC:

43412

AN:

67872

Other (OTH)

AF:

0.552

AC:

1164

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1613

3226

4839

6452

8065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.594

Hom.:

75614

Bravo

AF:

0.501

Asia WGS

AF:

0.531

AC:

1844

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.7

(source)

DANN

Benign

0.79

PhyloP100

0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over