rs2247208

Variant names:

• chr1-204908524-G-A
• rs2247208
• NM_001005388.3:c.-199-12108G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-204908524-G-A
• chr1-204908524-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005388.3(NFASC):​c.-199-12108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,016 control chromosomes in the GnomAD database, including 60,515 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (60515 hom., cov: 31)
• Consequence: NFASC NM_001005388.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with central and peripheral motor dysfunction

  Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFASC	NM_001005388.3	c.-199-12108G>A		intron_variant	Intron 1 of 29	ENST00000339876.11	NP_001005388.2
NFASC	NM_001160331.2	c.-90-35702G>A		intron_variant	Intron 1 of 27	ENST00000539706.6	NP_001153803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFASC	ENST00000339876.11	c.-199-12108G>A		intron_variant	Intron 1 of 29	5	NM_001005388.3	ENSP00000344786.6
NFASC	ENST00000539706.6	c.-90-35702G>A		intron_variant	Intron 1 of 27	5	NM_001160331.2	ENSP00000438614.2

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135255 AN: 151898 Hom.: 60460 Cov.: 31

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.896

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.890 AC: 135370 AN: 152016 Hom.: 60515 Cov.: 31 AF XY: 0.886 AC XY: 65844 AN XY: 74304

African (AFR) AF: 0.962 AC: 39925 AN: 41484

American (AMR) AF: 0.908 AC: 13869 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2983 AN: 3472

East Asian (EAS) AF: 0.801 AC: 4141 AN: 5170

South Asian (SAS) AF: 0.775 AC: 3734 AN: 4818

European-Finnish (FIN) AF: 0.826 AC: 8684 AN: 10516

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59135 AN: 67956

Other (OTH) AF: 0.896 AC: 1894 AN: 2114

Alfa AF: 0.877 Hom.: 66771

Bravo AF: 0.903

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.30
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2247208; hg19: chr1-204877652; COSMIC: COSV58362026;