rs9324014

Variant names:

• chr14-99746972-G-A
• rs9324014
• ENST00000554479.5:c.28+9112G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-99746972-G-A
• chr14-99746972-G-C
• chr14-99746972-G-T

Variant summary

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

The NM_001375411.1(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 NM_001375411.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 6 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: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375411.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML1	NM_001375411.1		c.28+9112G>A		intron	N/A	NP_001362340.1
	EML1	NM_001440377.1		c.28+9112G>A		intron	N/A	NP_001427306.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML1	ENST00000554479.5	TSL:1	c.28+9112G>A		intron	N/A	ENSP00000451346.1	G3V3N9
	EML1	ENST00000555145.5	TSL:4	c.28+9112G>A		intron	N/A	ENSP00000452160.1	G3V538

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78850 AN: 151634 Hom.: 23208 Cov.: 30

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.: 30 AF XY: 0.525 AC XY: 38942 AN XY: 74124

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.79
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs9324014; hg19: chr14-100213309;