rs12590101

Positions:

• chr14-88629506-C-G

Variant summary

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

The NM_183387.3(EML5):​c.4358-1687G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,086 control chromosomes in the GnomAD database, including 3,083 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 0.18 (3083 hom., cov: 32)
• Consequence: EML5 NM_183387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

Genes affected

EML5 (HGNC:18197): (EMAP like 5) Predicted to enable microtubule binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML5	NM_183387.3	c.4358-1687G>C		intron_variant		ENST00000554922.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML5	ENST00000554922.6	c.4358-1687G>C		intron_variant		5	NM_183387.3	P4

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27825 AN: 151968 Hom.: 3076 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.183 AC: 27860 AN: 152086 Hom.: 3083 Cov.: 32 AF XY: 0.188 AC XY: 14010 AN XY: 74342

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.208

Alfa AF: 0.167 Hom.: 315

Bravo AF: 0.203

Asia WGS AF: 0.342 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.57

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: rs12590101; hg19: chr14-89095850;