NFIA p.Thr471Thr

Variant names:

• chr1-61406717-C-C
• ENST00000403491.8:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-61406718--
• chr1-61406720-G-T
• chr1-61406720-G-C
• chr1-61406720-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001134673.4(NFIA):​c. variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.80
• Publications: 0 publications found

Genes affected

NFIA (HGNC:7784): (nuclear factor I A) This gene encodes a member of the NF1 (nuclear factor 1) family of transcription factors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

NFIA Gene-Disease associations (from GenCC):

• brain malformations with or without urinary tract defects

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• chromosome 1p32-p31 deletion syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134673.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	NM_001134673.4	MANE Select	c.		intron	N/A	NP_001128145.1	Q12857-1
	NFIA	NM_001145512.2		c.		intron	N/A	NP_001138984.1	Q12857-4
	NFIA	NM_001145511.2		c.		intron	N/A	NP_001138983.1	Q12857-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	ENST00000403491.8	TSL:1 MANE Select	c.		exon_region	Exon 9 of 11	ENSP00000384523.3	Q12857-1
	NFIA	ENST00000371187.7	TSL:1	c.		exon_region	Exon 9 of 10	ENSP00000360229.3	Q12857-2
	NFIA	ENST00000493627.1	TSL:1	c.		exon_region	Exon 1 of 3	ENSP00000474817.1	S4R3W6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-61872389;