rs9324014

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
EML1	NM_001375411.1	c.28+9112G>A		intron_variant
EML1	XM_005267398.3	c.28+9112G>A		intron_variant
EML1	XM_047431068.1	c.28+9112G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML1	ENST00000554479.5	c.28+9112G>A		intron_variant		1
EML1	ENST00000555145.5	c.28+9112G>A		intron_variant		4

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

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.552

Alfa AF: 0.620 Hom.: 47591

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
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9324014; hg19: chr14-100213309;