rs17099050

Variant names:

• chr14-99789586-T-G
• rs17099050
• ENST00000554479.5:c.28+51726T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000554479.5(EML1):​c.28+51726T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,224 control chromosomes in the GnomAD database, including 1,979 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 0.12 (1979 hom., cov: 33)
• Consequence: EML1 ENST00000554479.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 4 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EML1	NM_001375411.1	c.28+51726T>G		intron_variant	Intron 1 of 21		NP_001362340.1
EML1	NM_001440377.1	c.28+51726T>G		intron_variant	Intron 1 of 20		NP_001427306.1
EML1	XM_005267398.3	c.28+51726T>G		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	c.28+51726T>G		intron_variant	Intron 1 of 10	1		ENSP00000451346.1
EML1	ENST00000327921.13	c.-27+15573T>G		intron_variant	Intron 1 of 22	2		ENSP00000327384.9
EML1	ENST00000555145.5	c.28+51726T>G		intron_variant	Intron 1 of 4	4		ENSP00000452160.1
EML1	ENST00000556199.1	c.-20+15573T>G		intron_variant	Intron 1 of 2	4		ENSP00000451991.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18138 AN: 152106 Hom.: 1975 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.119 AC: 18157 AN: 152224 Hom.: 1979 Cov.: 33 AF XY: 0.116 AC XY: 8652 AN XY: 74428

African (AFR) AF: 0.287 AC: 11888 AN: 41480

American (AMR) AF: 0.0749 AC: 1146 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3472

East Asian (EAS) AF: 0.0642 AC: 333 AN: 5188

South Asian (SAS) AF: 0.0521 AC: 251 AN: 4818

European-Finnish (FIN) AF: 0.0347 AC: 368 AN: 10618

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0538 AC: 3658 AN: 68024

Other (OTH) AF: 0.108 AC: 229 AN: 2116

Alfa AF: 0.0677 Hom.: 1559

Bravo AF: 0.129

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.70
DANN	Benign	0.76
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17099050; hg19: chr14-100255923;