14-88745629-C-G

Position:

• chr14-88745629-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.456+556G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,002 control chromosomes in the GnomAD database, including 4,484 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 0.24 (4484 hom., cov: 32)
• Consequence: EML5 NM_183387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML5	NM_183387.3	c.456+556G>C		intron_variant		ENST00000554922.6	NP_899243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML5	ENST00000554922.6	c.456+556G>C		intron_variant		5	NM_183387.3	ENSP00000451998.1
EML5	ENST00000380664.9	c.456+556G>C		intron_variant		5		ENSP00000370039.5

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36043 AN: 151884 Hom.: 4475 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.237 AC: 36087 AN: 152002 Hom.: 4484 Cov.: 32 AF XY: 0.235 AC XY: 17475 AN XY: 74262

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.213

Alfa AF: 0.0971 Hom.: 161

Bravo AF: 0.235

Asia WGS AF: 0.286 AC: 991 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.039
DANN	Benign	0.74

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: rs17260415; hg19: chr14-89211973; COSMIC: COSV61351560;