Variant 3-325956-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000256509.7(CHL1):c.92-3T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,595,674 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 19 hom. )

Consequence

CHL1
ENST00000256509.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.06705

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

CHL1 (HGNC:1939): (cell adhesion molecule L1 like) The protein encoded by this gene is a member of the L1 gene family of neural cell adhesion molecules. It is a neural recognition molecule that may be involved in signal transduction pathways. The deletion of one copy of this gene may be responsible for mental defects in patients with 3p- syndrome. This protein may also play a role in the growth of certain cancers. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Nov 2011]

CHL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 3-325956-T-A is Benign according to our data. Variant chr3-325956-T-A is described in ClinVar as [Benign]. Clinvar id is 773668.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHL1	NM_006614.4 linkuse as main transcript	c.92-3T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000256509.7	NP_006605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7 linkuse as main transcript	c.92-3T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006614.4	ENSP00000256509	P3	O00533-2

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

272

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00599

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00237

AC:

582

AN:

245998

Hom.:

AF XY:

0.00230

AC XY:

306

AN XY:

133156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000202

Gnomad EAS exome

AF:

0.00441

Gnomad SAS exome

AF:

0.000269

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.000857

Gnomad OTH exome

AF:

0.00253

GnomAD4 exome

AF:

0.00119

AC:

1712

AN:

1443490

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

839

AN XY:

718920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000464

Gnomad4 EAS exome

AF:

0.00691

Gnomad4 SAS exome

AF:

0.000341

Gnomad4 FIN exome

AF:

0.0165

Gnomad4 NFE exome

AF:

0.000385

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00179

AC:

272

AN:

152184

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00600

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.0179

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000833

Hom.:

Bravo

AF:

0.000491

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000111

EpiControl

AF:

0.000120

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CHL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.067

dbscSNV1_RF

Benign

0.39

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 11

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