chr9-23817550-A-G

Variant names:

• chr9-23817550-A-G
• rs17551174
• NM_004432.5:c.-16+8256T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004432.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL2	NM_004432.5	MANE Select	c.-16+8256T>C		intron	N/A	NP_004423.2
	ELAVL2	NM_001351455.2		c.-20+8256T>C		intron	N/A	NP_001338384.1
	ELAVL2	NM_001385697.1		c.-20+5216T>C		intron	N/A	NP_001372626.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL2	ENST00000397312.7	TSL:1 MANE Select	c.-16+8256T>C		intron	N/A	ENSP00000380479.2
	ELAVL2	ENST00000380117.5	TSL:1	c.-13+8256T>C		intron	N/A	ENSP00000369460.1
	ELAVL2	ENST00000223951.10	TSL:1	c.-16+3677T>C		intron	N/A	ENSP00000223951.5

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

African (AFR) AF: 0.0349 AC: 1452 AN: 41560

American (AMR) AF: 0.133 AC: 2041 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3470

East Asian (EAS) AF: 0.141 AC: 728 AN: 5174

South Asian (SAS) AF: 0.155 AC: 749 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2357 AN: 10586

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10730 AN: 67996

Other (OTH) AF: 0.146 AC: 309 AN: 2114

Alfa AF: 0.147 Hom.: 4906

Bravo AF: 0.114

Asia WGS AF: 0.118 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.28
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17551174; hg19: chr9-23817548;