14-99865318-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004434.3(EML1):c.251-196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,072 control chromosomes in the GnomAD database, including 5,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (5834 hom., cov: 32)
• Consequence: EML1 NM_004434.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-99865318-G-A is Benign according to our data. Variant chr14-99865318-G-A is described in ClinVar as [Benign]. Clinvar id is 1239132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML1	NM_004434.3	c.251-196G>A		intron_variant		ENST00000262233.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML1	ENST00000262233.11	c.251-196G>A		intron_variant		1	NM_004434.3	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40334 AN: 151954 Hom.: 5828 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.265 AC: 40358 AN: 152072 Hom.: 5834 Cov.: 32 AF XY: 0.264 AC XY: 19599 AN XY: 74318

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.266

Alfa AF: 0.291 Hom.: 850

Bravo AF: 0.251

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs12432209; hg19: chr14-100331655;