rs3745816

Variant names:

• chr19-45609649-C-T
• rs3745816
• NM_012155.4:c.*14G>A

Variant summary

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

The NM_012155.4(EML2):​c.*14G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,590,846 control chromosomes in the GnomAD database, including 2,650 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 0.077 (1018 hom., cov: 31)
  • Exomes 𝑓: 0.029 (1632 hom.)
• Consequence: EML2 NM_012155.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EML2	NM_012155.4	c.*14G>A		3_prime_UTR_variant	Exon 19 of 19	ENST00000245925.8	NP_036287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML2	ENST00000245925	c.*14G>A		3_prime_UTR_variant	Exon 19 of 19	1	NM_012155.4	ENSP00000245925.3

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11649 AN: 151778 Hom.: 1015 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.00717

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0722

GnomAD3 exomes AF: 0.0434 AC: 10131 AN: 233640 Hom.: 594 AF XY: 0.0432 AC XY: 5494 AN XY: 127216

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.0195

Gnomad ASJ exome AF: 0.0360

Gnomad EAS exome AF: 0.0331

Gnomad SAS exome AF: 0.0966

Gnomad FIN exome AF: 0.00713

Gnomad NFE exome AF: 0.0199

Gnomad OTH exome AF: 0.0377

GnomAD4 exome AF: 0.0294 AC: 42253 AN: 1438952 Hom.: 1632 Cov.: 31 AF XY: 0.0311 AC XY: 22215 AN XY: 714932

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.0230

Gnomad4 ASJ exome AF: 0.0341

Gnomad4 EAS exome AF: 0.0326

Gnomad4 SAS exome AF: 0.0966

Gnomad4 FIN exome AF: 0.00843

Gnomad4 NFE exome AF: 0.0189

Gnomad4 OTH exome AF: 0.0398

GnomAD4 genome AF: 0.0769 AC: 11677 AN: 151894 Hom.: 1018 Cov.: 31 AF XY: 0.0763 AC XY: 5664 AN XY: 74248

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.0374

Gnomad4 SAS AF: 0.0970

Gnomad4 FIN AF: 0.00717

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0340 Hom.: 272

Bravo AF: 0.0853

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.68

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: rs3745816; hg19: chr19-46112907;