Variant 18-37274304-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_020180.4(CELF4):c.801+7G>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 0.0148 in 1,611,006 control chromosomes in the GnomAD database, including 266 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 0.012 ( 30 hom., cov: 33)

Exomes 𝑓: 0.015 ( 236 hom. )

Consequence

CELF4
NM_020180.4 splice_region, intron

Scores

Splicing: ADA: 0.0007900

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.786

Variant links:

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]

CELF4 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 18-37274304-C-T is Benign according to our data. Variant chr18-37274304-C-T is described in ClinVar as [Benign]. Clinvar id is 3037495.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0123 (1874/152378) while in subpopulation NFE AF= 0.0192 (1306/68038). AF 95% confidence interval is 0.0183. There are 30 homozygotes in gnomad4. There are 897 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd at 1876 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF4	NM_020180.4 linkuse as main transcript	c.801+7G>A		splice_region_variant, intron_variant		ENST00000420428.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF4	ENST00000420428.7 linkuse as main transcript	c.801+7G>A		splice_region_variant, intron_variant		5	NM_020180.4	P4	Q9BZC1-1
	ENST00000588766.5 linkuse as main transcript	n.121+478C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1876

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00351

Gnomad FIN

AF:

0.0213

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0192

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0126

AC:

3114

AN:

246996

Hom.:

AF XY:

0.0127

AC XY:

1695

AN XY:

133990

show subpopulations

Gnomad AFR exome

AF:

0.00224

Gnomad AMR exome

AF:

0.00758

Gnomad ASJ exome

AF:

0.0303

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00346

Gnomad FIN exome

AF:

0.0218

Gnomad NFE exome

AF:

0.0166

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.0150

AC:

21899

AN:

1458628

Hom.:

236

Cov.:

AF XY:

0.0147

AC XY:

10692

AN XY:

725748

show subpopulations

Gnomad4 AFR exome

AF:

0.00247

Gnomad4 AMR exome

AF:

0.00807

Gnomad4 ASJ exome

AF:

0.0296

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00353

Gnomad4 FIN exome

AF:

0.0221

Gnomad4 NFE exome

AF:

0.0163

Gnomad4 OTH exome

AF:

0.0154

GnomAD4 genome

AF:

0.0123

AC:

1874

AN:

152378

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

897

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0213

Gnomad4 NFE

AF:

0.0192

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0174

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0159

EpiControl

AF:

0.0162

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CELF4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00079

dbscSNV1_RF

Benign

0.024

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over