1-61406543-GCCCC-G

Position:

• chr1-61406543-GCCCC-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001134673.4(NFIA):​c.1255-8_1255-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 875,344 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: NFIA NM_001134673.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIA	NM_001134673.4	c.1255-8_1255-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000403491.8
NFIA	NM_001145511.2	c.1231-8_1231-5del		splice_polypyrimidine_tract_variant, intron_variant
NFIA	NM_001145512.2	c.1390-8_1390-5del		splice_polypyrimidine_tract_variant, intron_variant
NFIA	NM_005595.5	c.1255-8_1255-5del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIA	ENST00000403491.8	c.1255-8_1255-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001134673.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000157 AC: 1 AN: 63834 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000328

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00127 AC: 70 AN: 55298 Hom.: 0 AF XY: 0.00118 AC XY: 36 AN XY: 30448

Gnomad AFR exome AF: 0.00170

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00135

Gnomad EAS exome AF: 0.00102

Gnomad SAS exome AF: 0.00181

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00111 AC: 898 AN: 811510 Hom.: 1 AF XY: 0.00115 AC XY: 467 AN XY: 406102

Gnomad4 AFR exome AF: 0.00222

Gnomad4 AMR exome AF: 0.00111

Gnomad4 ASJ exome AF: 0.000950

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.00130

Gnomad4 FIN exome AF: 0.000387

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.0000157 AC: 1 AN: 63834 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 29818

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000328

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs58081092; hg19: chr1-61872215;