1-61406553-C-CT

Variant names:

• chr1-61406553-C-CT
• rs777624713
• NM_001134673.4:c.1255-9_1255-8insT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001134673.4(NFIA):​c.1255-9_1255-8insT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000834 in 1,198,488 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: NFIA NM_001134673.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 10 AD gene.

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.1255-9_1255-8insT		splice_region intron	N/A	NP_001128145.1	Q12857-1
	NFIA	NM_001145512.2		c.1390-9_1390-8insT		splice_region intron	N/A	NP_001138984.1	Q12857-4
	NFIA	NM_001145511.2		c.1231-9_1231-8insT		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.1255-9_1255-8insT		splice_region intron	N/A	ENSP00000384523.3	Q12857-1
	NFIA	ENST00000371187.7	TSL:1	c.1255-9_1255-8insT		splice_region intron	N/A	ENSP00000360229.3	Q12857-2
	NFIA	ENST00000371189.8	TSL:2	c.1390-9_1390-8insT		splice_region intron	N/A	ENSP00000360231.3	Q12857-4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000834 AC: 10 AN: 1198488 Hom.: 0 Cov.: 24 AF XY: 0.0000168 AC XY: 10 AN XY: 595802

African (AFR) AF: 0.00 AC: 0 AN: 27040

American (AMR) AF: 0.0000309 AC: 1 AN: 32324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20276

East Asian (EAS) AF: 0.00 AC: 0 AN: 27052

South Asian (SAS) AF: 0.000117 AC: 8 AN: 68294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 927778

Other (OTH) AF: 0.0000208 AC: 1 AN: 48140

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17

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: rs777624713; hg19: chr1-61872225;