Variant 1-204952130-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001005388.3(NFASC):c.215+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,588,814 control chromosomes in the GnomAD database, including 140,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9796 hom., cov: 32)

Exomes 𝑓: 0.42 ( 130968 hom. )

Consequence

NFASC
NM_001005388.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.365

Variant links:

Genes affected

NFASC (HGNC:29866): (neurofascin) This gene encodes an L1 family immunoglobulin cell adhesion molecule with multiple IGcam and fibronectin domains. The protein functions in neurite outgrowth, neurite fasciculation, and organization of the axon initial segment (AIS) and nodes of Ranvier on axons during early development. Both the AIS and nodes of Ranvier contain high densities of voltage-gated Na+ (Nav) channels which are clustered by interactions with cytoskeletal and scaffolding proteins including this protein, gliomedin, ankyrin 3 (ankyrin-G), and betaIV spectrin. This protein links the AIS extracellular matrix to the intracellular cytoskeleton. This gene undergoes extensive alternative splicing, and the full-length nature of some variants has not been determined.[provided by RefSeq, May 2009]

NFASC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-204952130-A-G is Benign according to our data. Variant chr1-204952130-A-G is described in ClinVar as [Benign]. Clinvar id is 1325900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFASC	NM_001005388.3 linkuse as main transcript	c.215+14A>G		intron_variant		ENST00000339876.11	NP_001005388.2
NFASC	NM_001160331.2 linkuse as main transcript	c.197+14A>G		intron_variant		ENST00000539706.6	NP_001153803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFASC	ENST00000339876.11 linkuse as main transcript	c.215+14A>G		intron_variant		5	NM_001005388.3	ENSP00000344786		O94856-9
NFASC	ENST00000539706.6 linkuse as main transcript	c.197+14A>G		intron_variant		5	NM_001160331.2	ENSP00000438614	A2	O94856-11

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49872

AN:

151950

Hom.:

9798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.0822

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.342

GnomAD3 exomes

AF:

0.374

AC:

92826

AN:

248338

Hom.:

19076

AF XY:

0.384

AC XY:

51534

AN XY:

134094

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.318

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.0797

Gnomad SAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.419

Gnomad NFE exome

AF:

0.447

Gnomad OTH exome

AF:

0.407

GnomAD4 exome

AF:

0.418

AC:

601165

AN:

1436746

Hom.:

130968

Cov.:

AF XY:

0.420

AC XY:

300766

AN XY:

715908

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.316

Gnomad4 ASJ exome

AF:

0.429

Gnomad4 EAS exome

AF:

0.0790

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.429

Gnomad4 NFE exome

AF:

0.444

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.328

AC:

49880

AN:

152068

Hom.:

9796

Cov.:

AF XY:

0.325

AC XY:

24146

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.0820

Gnomad4 SAS

AF:

0.404

Gnomad4 FIN

AF:

0.409

Gnomad4 NFE

AF:

0.445

Gnomad4 OTH

AF:

0.339

Alfa

AF:

0.417

Hom.:

6982

Bravo

AF:

0.308

Asia WGS

AF:

0.232

AC:

808

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurodevelopmental disorder with central and peripheral motor dysfunction

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.5

DANN

Benign

0.76

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

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