14-99875093-A-G

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.384-3392A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 982,272 control chromosomes in the GnomAD database, including 69,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8281 hom., cov: 32)
  • Exomes 𝑓: 0.38 (60898 hom.)
• Consequence: EML1 NM_004434.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.115

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 14-99875093-A-G is Benign according to our data. Variant chr14-99875093-A-G is described in ClinVar as [Benign]. Clinvar id is 1241640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML1	NM_004434.3	c.384-3392A>G		intron_variant		ENST00000262233.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML1	ENST00000262233.11	c.384-3392A>G		intron_variant		1	NM_004434.3	P1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48142 AN: 151944 Hom.: 8271 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.380 AC: 315352 AN: 830210 Hom.: 60898 AF XY: 0.384 AC XY: 164781 AN XY: 429664

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.380

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.317 AC: 48150 AN: 152062 Hom.: 8281 Cov.: 32 AF XY: 0.322 AC XY: 23898 AN XY: 74330

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.366

Alfa AF: 0.367 Hom.: 21085

Bravo AF: 0.312

Asia WGS AF: 0.431 AC: 1499 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	2.8
Dann	Benign	0.72

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: rs1191121; hg19: chr14-100341430;