rs2247208

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NFASC	NM_001005388.3	c.-199-12108G>A		intron_variant		ENST00000339876.11
NFASC	NM_001160331.2	c.-90-35702G>A		intron_variant		ENST00000539706.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFASC	ENST00000339876.11	c.-199-12108G>A		intron_variant		5	NM_001005388.3
NFASC	ENST00000539706.6	c.-90-35702G>A		intron_variant		5	NM_001160331.2	A2

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

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.896

Alfa AF: 0.875 Hom.: 55875

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

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