chr1-61406543-G-GC

Position:

• chr1-61406543-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001134673.4(NFIA):​c.1255-5dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (46 hom., cov: 0)
  • Exomes 𝑓: 0.0066 (2 hom.)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 1-61406543-G-GC is Benign according to our data. Variant chr1-61406543-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 2638855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0208 (1325/63654) while in subpopulation NFE AF= 0.0253 (768/30376). AF 95% confidence interval is 0.0238. There are 46 homozygotes in gnomad4. There are 590 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1325 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 1326 AN: 63620 Hom.: 46 Cov.: 0

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.0240

Gnomad AMR AF: 0.0180

Gnomad ASJ AF: 0.0292

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0102

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0284

GnomAD3 exomes AF: 0.00184 AC: 102 AN: 55298 Hom.: 0 AF XY: 0.00174 AC XY: 53 AN XY: 30448

Gnomad AFR exome AF: 0.000568

Gnomad AMR exome AF: 0.00499

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000679

Gnomad SAS exome AF: 0.00363

Gnomad FIN exome AF: 0.000877

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00658 AC: 5347 AN: 813002 Hom.: 2 Cov.: 0 AF XY: 0.00692 AC XY: 2816 AN XY: 406884

Gnomad4 AFR exome AF: 0.00525

Gnomad4 AMR exome AF: 0.00696

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.00887

Gnomad4 SAS exome AF: 0.00860

Gnomad4 FIN exome AF: 0.00717

Gnomad4 NFE exome AF: 0.00620

Gnomad4 OTH exome AF: 0.00782

GnomAD4 genome AF: 0.0208 AC: 1325 AN: 63654 Hom.: 46 Cov.: 0 AF XY: 0.0198 AC XY: 590 AN XY: 29758

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0180

Gnomad4 ASJ AF: 0.0292

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0253

Gnomad4 OTH AF: 0.0282

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

NFIA: PM2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;