18-37266555-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_020180.4(CELF4):c.1143C>T(p.Ala381=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,597,166 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (5 hom.)
• Consequence: CELF4 NM_020180.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.23

Genes affected

CELF4 (HGNC:14015): (CUGBP Elav-like family member 4) Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 18-37266555-G-A is Benign according to our data. Variant chr18-37266555-G-A is described in ClinVar as [Benign]. Clinvar id is 718289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.23 with no splicing effect.
• BS2: High AC in GnomAd at 277 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF4	NM_020180.4	c.1143C>T	p.Ala381=	synonymous_variant	9/13	ENST00000420428.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF4	ENST00000420428.7	c.1143C>T	p.Ala381=	synonymous_variant	9/13	5	NM_020180.4	P4

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00334

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00165 AC: 365 AN: 221296 Hom.: 1 AF XY: 0.00168 AC XY: 200 AN XY: 118802

Gnomad AFR exome AF: 0.000569

Gnomad AMR exome AF: 0.000779

Gnomad ASJ exome AF: 0.00127

Gnomad EAS exome AF: 0.0000611

Gnomad SAS exome AF: 0.000112

Gnomad FIN exome AF: 0.0000547

Gnomad NFE exome AF: 0.00304

Gnomad OTH exome AF: 0.00217

GnomAD4 exome AF: 0.00299 AC: 4313 AN: 1444812 Hom.: 5 Cov.: 31 AF XY: 0.00290 AC XY: 2081 AN XY: 716780

Gnomad4 AFR exome AF: 0.000509

Gnomad4 AMR exome AF: 0.000843

Gnomad4 ASJ exome AF: 0.00144

Gnomad4 EAS exome AF: 0.0000512

Gnomad4 SAS exome AF: 0.000121

Gnomad4 FIN exome AF: 0.0000574

Gnomad4 NFE exome AF: 0.00366

Gnomad4 OTH exome AF: 0.00264

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.00156 AC XY: 116 AN XY: 74496

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.000522

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00334

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00265 Hom.: 1

Bravo AF: 0.00189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	1.2
Dann	Benign	0.91

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: rs145042940; hg19: chr18-34846518;