1-61406543-GCCCC-GCCCCCC

Position:

• chr1-61406543-GCCCC-GCCCCCC

Variant summary

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

The NM_001134673.4(NFIA):​c.1255-6_1255-5dupCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00069 (1 hom.)
• Consequence: NFIA NM_001134673.4 splice_region, 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]

NFIA (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 109 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.1255-6_1255-5dupCC		splice_region_variant, intron_variant		ENST00000403491.8	NP_001128145.1
NFIA	NM_001145512.2	c.1390-6_1390-5dupCC		splice_region_variant, intron_variant			NP_001138984.1
NFIA	NM_001145511.2	c.1231-6_1231-5dupCC		splice_region_variant, intron_variant			NP_001138983.1
NFIA	NM_005595.5	c.1255-6_1255-5dupCC		splice_region_variant, intron_variant			NP_005586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.1255-6_1255-5dupCC		splice_region_variant, intron_variant		1	NM_001134673.4	ENSP00000384523.3

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 109 AN: 63774 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00110

Gnomad AMI AF: 0.00217

Gnomad AMR AF: 0.00104

Gnomad ASJ AF: 0.000559

Gnomad EAS AF: 0.00138

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.00122

GnomAD3 exomes AF: 0.0000904 AC: 5 AN: 55298 Hom.: 0 AF XY: 0.000131 AC XY: 4 AN XY: 30448

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000146

Gnomad NFE exome AF: 0.0000850

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000695 AC: 565 AN: 813270 Hom.: 1 Cov.: 0 AF XY: 0.000727 AC XY: 296 AN XY: 407028

Gnomad4 AFR exome AF: 0.000539

Gnomad4 AMR exome AF: 0.000580

Gnomad4 ASJ exome AF: 0.000510

Gnomad4 EAS exome AF: 0.00146

Gnomad4 SAS exome AF: 0.000752

Gnomad4 FIN exome AF: 0.000684

Gnomad4 NFE exome AF: 0.000671

Gnomad4 OTH exome AF: 0.000862

GnomAD4 genome AF: 0.00171 AC: 109 AN: 63808 Hom.: 1 Cov.: 0 AF XY: 0.00174 AC XY: 52 AN XY: 29812

Gnomad4 AFR AF: 0.00110

Gnomad4 AMR AF: 0.00104

Gnomad4 ASJ AF: 0.000559

Gnomad4 EAS AF: 0.00138

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00107

Gnomad4 NFE AF: 0.00243

Gnomad4 OTH AF: 0.00121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;