rs10141863

chr14-99810370-G-Achr14-99810370-G-C

Variant summary

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

The NM_004434.3(EML1):c.67+16827G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,054 control chromosomes in the GnomAD database, including 12,909 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 0.40 (12909 hom., cov: 32)
• Consequence: EML1 NM_004434.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML1	NM_004434.3	c.67+16827G>A		intron_variant		ENST00000262233.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML1	ENST00000262233.11	c.67+16827G>A		intron_variant		1	NM_004434.3	P1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60546 AN: 151936 Hom.: 12897 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.399 AC: 60595 AN: 152054 Hom.: 12909 Cov.: 32 AF XY: 0.405 AC XY: 30130 AN XY: 74306

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.418

Alfa AF: 0.453 Hom.: 32339

Bravo AF: 0.389

Asia WGS AF: 0.458 AC: 1596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.037
Dann	Benign	0.60

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: rs10141863; hg19: chr14-100276707;