rs4445998

chr19-45613529-C-T

Variant summary

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

The NM_012155.4(EML2):c.1824+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,613,418 control chromosomes in the GnomAD database, including 1,842 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 0.058 (553 hom., cov: 32)
  • Exomes 𝑓: 0.028 (1289 hom.)
• Consequence: EML2 NM_012155.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

Genes affected

EML2 (HGNC:18035): (EMAP like 2) Enables microtubule binding activity. Involved in negative regulation of microtubule polymerization and regulation of microtubule nucleation. Colocalizes with mitotic spindle. [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 (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EML2	NM_012155.4	c.1824+12G>A		intron_variant		ENST00000245925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EML2	ENST00000245925.8	c.1824+12G>A		intron_variant		1	NM_012155.4	A1

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8871 AN: 152056 Hom.: 553 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.0376

Gnomad SAS AF: 0.0964

Gnomad FIN AF: 0.00716

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0195

Gnomad OTH AF: 0.0498

GnomAD3 exomes AF: 0.0385 AC: 9646 AN: 250856 Hom.: 464 AF XY: 0.0398 AC XY: 5402 AN XY: 135580

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.0366

Gnomad EAS exome AF: 0.0339

Gnomad SAS exome AF: 0.0976

Gnomad FIN exome AF: 0.00710

Gnomad NFE exome AF: 0.0197

Gnomad OTH exome AF: 0.0373

GnomAD4 exome AF: 0.0278 AC: 40672 AN: 1461244 Hom.: 1289 Cov.: 31 AF XY: 0.0298 AC XY: 21628 AN XY: 726900

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.0182

Gnomad4 ASJ exome AF: 0.0344

Gnomad4 EAS exome AF: 0.0333

Gnomad4 SAS exome AF: 0.0977

Gnomad4 FIN exome AF: 0.00838

Gnomad4 NFE exome AF: 0.0189

Gnomad4 OTH exome AF: 0.0352

GnomAD4 genome AF: 0.0584 AC: 8880 AN: 152174 Hom.: 553 Cov.: 32 AF XY: 0.0584 AC XY: 4349 AN XY: 74408

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.0379

Gnomad4 SAS AF: 0.0969

Gnomad4 FIN AF: 0.00716

Gnomad4 NFE AF: 0.0195

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0275 Hom.: 124

Bravo AF: 0.0635

Asia WGS AF: 0.0480 AC: 167 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	0.010
Dann	Benign	0.58

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: rs4445998; hg19: chr19-46116787;