14-99751945-G-C

Variant names:

• chr14-99751945-G-C
• rs10148112
• ENST00000554479.5:c.28+14085G>C

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+14085G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,912 control chromosomes in the GnomAD database, including 22,267 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 (22267 hom., cov: 31)
• Consequence: EML1 NM_001375411.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67
• Publications: 0 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: ClinGen, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 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+14085G>C		intron	N/A	NP_001362340.1
	EML1	NM_001440377.1		c.28+14085G>C		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+14085G>C		intron	N/A	ENSP00000451346.1	G3V3N9
	EML1	ENST00000555145.5	TSL:4	c.28+14085G>C		intron	N/A	ENSP00000452160.1	G3V538

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79638 AN: 151790 Hom.: 22248 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.525 AC: 79698 AN: 151912 Hom.: 22267 Cov.: 31 AF XY: 0.529 AC XY: 39249 AN XY: 74228

African (AFR) AF: 0.310 AC: 12827 AN: 41408

American (AMR) AF: 0.592 AC: 9041 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2118 AN: 3468

East Asian (EAS) AF: 0.499 AC: 2568 AN: 5146

South Asian (SAS) AF: 0.529 AC: 2539 AN: 4800

European-Finnish (FIN) AF: 0.692 AC: 7312 AN: 10570

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41383 AN: 67940

Other (OTH) AF: 0.544 AC: 1147 AN: 2110

Alfa AF: 0.422 Hom.: 1231

Bravo AF: 0.511

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.089
DANN	Benign	0.35
PhyloP100		-2.7

Splicing

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

Other links and lift over

dbSNP: rs10148112; hg19: chr14-100218282;