NM_183387.3:c.357+2041A>G

Variant names:

• chr14-88752471-T-C
• rs12880096
• NM_183387.3:c.357+2041A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183387.3(EML5):​c.357+2041A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,044 control chromosomes in the GnomAD database, including 33,108 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 0.64 (33108 hom., cov: 32)
• Consequence: EML5 NM_183387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EML5	NM_183387.3	c.357+2041A>G		intron_variant	Intron 2 of 43	ENST00000554922.6	NP_899243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML5	ENST00000554922.6	c.357+2041A>G		intron_variant	Intron 2 of 43	5	NM_183387.3	ENSP00000451998.1
EML5	ENST00000380664.9	c.357+2041A>G		intron_variant	Intron 2 of 41	5		ENSP00000370039.5

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97119 AN: 151926 Hom.: 33040 Cov.: 32

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.640 AC: 97241 AN: 152044 Hom.: 33108 Cov.: 32 AF XY: 0.638 AC XY: 47428 AN XY: 74300

African (AFR) AF: 0.854 AC: 35460 AN: 41500

American (AMR) AF: 0.659 AC: 10055 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1861 AN: 3468

East Asian (EAS) AF: 0.937 AC: 4856 AN: 5184

South Asian (SAS) AF: 0.674 AC: 3251 AN: 4820

European-Finnish (FIN) AF: 0.465 AC: 4900 AN: 10548

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34848 AN: 67956

Other (OTH) AF: 0.589 AC: 1243 AN: 2110

Alfa AF: 0.591 Hom.: 5420

Bravo AF: 0.666

Asia WGS AF: 0.799 AC: 2778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.49
DANN	Benign	0.63
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12880096; hg19: chr14-89218815;