rs6716767

Positions:

• chr2-42332116-A-C

Variant summary

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

The ENST00000318522.10(EML4):​c.*1909A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 220,898 control chromosomes in the GnomAD database, including 2,543 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 0.15 (2014 hom., cov: 32)
  • Exomes 𝑓: 0.12 (529 hom.)
• Consequence: EML4 ENST00000318522.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

Genes affected

EML4 (HGNC:1316): (EMAP like 4) This gene is a member of the echinoderm microtubule associated protein-like family. The encoded WD-repeat protein may be involved in microtubule formation. Abnormal fusion of parts of this gene with portions of the anaplastic lymphoma receptor tyrosine kinase gene, which generates EML4-ALK fusion transcripts, is one of the primary mutations associated with non-small cell lung cancer. Alternative splicing of this gene results in two transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EML4	NM_019063.5	c.*1909A>C		3_prime_UTR_variant	23/23	ENST00000318522.10	NP_061936.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EML4	ENST00000318522.10	c.*1909A>C		3_prime_UTR_variant	23/23	1	NM_019063.5	ENSP00000320663	P3
EML4	ENST00000406175.3	n.4190A>C		non_coding_transcript_exon_variant	14/14	1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23075 AN: 152078 Hom.: 2009 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0292

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.116 AC: 7938 AN: 68704 Hom.: 529 Cov.: 0 AF XY: 0.115 AC XY: 3643 AN XY: 31816

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0915

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0416

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.152 AC: 23110 AN: 152194 Hom.: 2014 Cov.: 32 AF XY: 0.154 AC XY: 11449 AN XY: 74414

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.0940

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0287

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.175

Alfa AF: 0.129 Hom.: 1967

Bravo AF: 0.148

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.4
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs6716767; hg19: chr2-42559256;