NM_001419.3:c.431-6G>A

Variant names:

• chr19-7967796-C-T
• rs1077340
• NM_001419.3:c.431-6G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001419.3(ELAVL1):​c.431-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,606,192 control chromosomes in the GnomAD database, including 60,035 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6150 hom., cov: 33)
  • Exomes 𝑓: 0.27 (53885 hom.)
• Consequence: ELAVL1 NM_001419.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001073
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.109
• Publications: 12 publications found

Genes affected

ELAVL1 (HGNC:3312): (ELAV like RNA binding protein 1) The protein encoded by this gene is a member of the ELAVL family of RNA-binding proteins that contain several RNA recognition motifs, and selectively bind AU-rich elements (AREs) found in the 3' untranslated regions of mRNAs. AREs signal degradation of mRNAs as a means to regulate gene expression, thus by binding AREs, the ELAVL family of proteins play a role in stabilizing ARE-containing mRNAs. This gene has been implicated in a variety of biological processes and has been linked to a number of diseases, including cancer. It is highly expressed in many cancers, and could be potentially useful in cancer diagnosis, prognosis, and therapy. [provided by RefSeq, Sep 2012]

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 19-7967796-C-T is Benign according to our data. Variant chr19-7967796-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001419.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL1	NM_001419.3	MANE Select	c.431-6G>A		splice_region intron	N/A	NP_001410.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL1	ENST00000407627.7	TSL:1 MANE Select	c.431-6G>A		splice_region intron	N/A	ENSP00000385269.1	Q15717-1
	ELAVL1	ENST00000958865.1		c.707-6G>A		splice_region intron	N/A	ENSP00000628924.1
	ELAVL1	ENST00000596459.5	TSL:2	c.431-6G>A		splice_region intron	N/A	ENSP00000472197.1	Q15717-1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42013 AN: 151932 Hom.: 6140 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.278

GnomAD2 exomes AF: 0.229 AC: 56464 AN: 247060 AF XY: 0.228

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.0692

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.265 AC: 385465 AN: 1454142 Hom.: 53885 Cov.: 36 AF XY: 0.261 AC XY: 188811 AN XY: 722378

African (AFR) AF: 0.344 AC: 11378 AN: 33106

American (AMR) AF: 0.146 AC: 6372 AN: 43684

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 7363 AN: 25908

East Asian (EAS) AF: 0.0683 AC: 2699 AN: 39544

South Asian (SAS) AF: 0.131 AC: 11241 AN: 85512

European-Finnish (FIN) AF: 0.252 AC: 13422 AN: 53312

Middle Eastern (MID) AF: 0.271 AC: 1555 AN: 5736

European-Non Finnish (NFE) AF: 0.285 AC: 315801 AN: 1107294

Other (OTH) AF: 0.260 AC: 15634 AN: 60046

GnomAD4 genome AF: 0.277 AC: 42055 AN: 152050 Hom.: 6150 Cov.: 33 AF XY: 0.271 AC XY: 20144 AN XY: 74302

African (AFR) AF: 0.338 AC: 14022 AN: 41450

American (AMR) AF: 0.207 AC: 3168 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3472

East Asian (EAS) AF: 0.0742 AC: 384 AN: 5176

South Asian (SAS) AF: 0.111 AC: 537 AN: 4824

European-Finnish (FIN) AF: 0.239 AC: 2523 AN: 10556

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19402 AN: 67980

Other (OTH) AF: 0.275 AC: 581 AN: 2110

Alfa AF: 0.279 Hom.: 18035

Bravo AF: 0.277

Asia WGS AF: 0.118 AC: 409 AN: 3478

EpiCase AF: 0.286

EpiControl AF: 0.287

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.7
DANN	Benign	0.80
PhyloP100		0.11
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.010		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: rs1077340; hg19: chr19-8032680; COSMIC: COSV60966054;