1-61406543-GCCCCCCCC-GCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC

Variant names:

• chr1-61406543-G-GCCCCCCCCCCCCCCCCCCCCCCC
• rs58081092
• NM_001134673.4:c.1255-5_1255-4insCCCCCCCCCCCCCCCCCCCCCCC

Variant summary

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

The NM_001134673.4(NFIA):​c.1255-5_1255-4insCCCCCCCCCCCCCCCCCCCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: NFIA NM_001134673.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886
• 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: Illumina, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.1255-5_1255-4insCCCCCCCCCCCCCCCCCCCCCCC		splice_region intron	N/A	NP_001128145.1	Q12857-1
	NFIA	NM_001145512.2		c.1390-5_1390-4insCCCCCCCCCCCCCCCCCCCCCCC		splice_region intron	N/A	NP_001138984.1	Q12857-4
	NFIA	NM_001145511.2		c.1231-5_1231-4insCCCCCCCCCCCCCCCCCCCCCCC		splice_region 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.1255-19_1255-18insCCCCCCCCCCCCCCCCCCCCCCC		intron	N/A	ENSP00000384523.3	Q12857-1
	NFIA	ENST00000371187.7	TSL:1	c.1255-19_1255-18insCCCCCCCCCCCCCCCCCCCCCCC		intron	N/A	ENSP00000360229.3	Q12857-2
	NFIA	ENST00000371189.8	TSL:2	c.1390-19_1390-18insCCCCCCCCCCCCCCCCCCCCCCC		intron	N/A	ENSP00000360231.3	Q12857-4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000123 AC: 1 AN: 813532 Hom.: 0 Cov.: 0 AF XY: 0.00000246 AC XY: 1 AN XY: 407170

African (AFR) AF: 0.00 AC: 0 AN: 18556

American (AMR) AF: 0.00 AC: 0 AN: 20702

Ashkenazi Jewish (ASJ) AF: 0.0000729 AC: 1 AN: 13726

East Asian (EAS) AF: 0.00 AC: 0 AN: 19860

South Asian (SAS) AF: 0.00 AC: 0 AN: 47852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 623550

Other (OTH) AF: 0.00 AC: 0 AN: 32508

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89

Splicing

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

Other links and lift over

dbSNP: rs58081092; hg19: chr1-61872215;