rs17551174

Positions:

• chr9-23817550-A-G

Variant summary

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

The NM_004432.5(ELAVL2):​c.-16+8256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,220 control chromosomes in the GnomAD database, including 1,514 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 0.13 (1514 hom., cov: 32)
• Consequence: ELAVL2 NM_004432.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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]

ELAVL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAVL2	NM_004432.5	c.-16+8256T>C		intron_variant		ENST00000397312.7	NP_004423.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAVL2	ENST00000397312.7	c.-16+8256T>C		intron_variant		1	NM_004432.5	ENSP00000380479.2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19220 AN: 152102 Hom.: 1516 Cov.: 32

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.126 AC: 19219 AN: 152220 Hom.: 1514 Cov.: 32 AF XY: 0.132 AC XY: 9828 AN XY: 74420

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.146

Alfa AF: 0.157 Hom.: 3184

Bravo AF: 0.114

Asia WGS AF: 0.118 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.28

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: rs17551174; hg19: chr9-23817548;