rs783562

chr9-23823401-G-Achr9-23823401-G-Cchr9-23823401-G-T

Variant summary

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

The NM_004432.5(ELAVL2):c.-16+2405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,964 control chromosomes in the GnomAD database, including 13,177 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 0.41 (13177 hom., cov: 32)
• Consequence: ELAVL2 NM_004432.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

Genes affected

ELAVL2 (HGNC:3313): (ELAV like RNA binding protein 2) In humans, the ELAV like RNA binding protein gene family has four members (ELAVL1-4). ELAVL RNA binding proteins recognize AU-rich elements in the 3' UTRs of gene transcripts and thereby regulate gene expression post-transcriptionally. The protein encoded by this gene binds to several 3' UTRs, including its own and also that of FOS, ID, and POU5F1. This gene encodes ELAVL2 and, like ELAVL3 and ELAVL4, is expressed specifically in neurons and primarily localizes to the cytoplasm. This protein also forms a cytosolic complex with the normally nuclear-localized ELAVL1 protein. Alternative splicing of this gene results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Jul 2020]

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 (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAVL2	NM_004432.5	c.-16+2405C>T		intron_variant		ENST00000397312.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAVL2	ENST00000397312.7	c.-16+2405C>T		intron_variant		1	NM_004432.5
ELAVL2	ENST00000380117.5	c.-13+2405C>T		intron_variant		1
ELAVL2	ENST00000462649.1	n.369+2405C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61955 AN: 151846 Hom.: 13122 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.408 AC: 62068 AN: 151964 Hom.: 13177 Cov.: 32 AF XY: 0.419 AC XY: 31093 AN XY: 74270

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.409

Alfa AF: 0.382 Hom.: 4742

Bravo AF: 0.412

Asia WGS AF: 0.552 AC: 1921 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	6.9
Dann	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs783562; hg19: chr9-23823399; COSMIC: COSV56369731; COSMIC: COSV56369731;