Variant 1-61081954-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_001145512.2(NFIA):c.11G>A(p.Cys4Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000572 in 1,398,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

NFIA
NM_001145512.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.256

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), NFIA. . Gene score misZ 3.231 (greater than the threshold 3.09). Trascript score misZ 3.286 (greater than threshold 3.09). GenCC has associacion of gene with chromosome 1p32-p31 deletion syndrome, brain malformations with or without urinary tract defects.

BP4

Computational evidence support a benign effect (MetaRNN=0.06252691).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIA	NM_001145512.2 linkuse as main transcript	c.11G>A	p.Cys4Tyr	missense_variant	1/12		NP_001138984.1
NFIA	NM_001145511.2 linkuse as main transcript	c.3+4326G>A		intron_variant			NP_001138983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
NFIA	ENST00000371189.8 linkuse as main transcript	c.11G>A	p.Cys4Tyr	missense_variant	1/12	2	ENSP00000360231	Q12857-4
NFIA	ENST00000371191.5 linkuse as main transcript	c.97-6195G>A		intron_variant		5	ENSP00000360233
NFIA	ENST00000407417.7 linkuse as main transcript	c.3+4326G>A		intron_variant		2	ENSP00000384680	Q12857-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000659

AC:

AN:

151654

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1398296

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689732

show subpopulations

Gnomad4 AFR exome

AF:

0.0000949

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.11G>A (p.C4Y) alteration is located in exon 1 (coding exon 1) of the NFIA gene. This alteration results from a G to A substitution at nucleotide position 11, causing the cysteine (C) at amino acid position 4 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.42

M_CAP

Benign

0.0058

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.020

REVEL

Benign

0.093

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.042

Vest4

0.15

MutPred

0.19

Gain of phosphorylation at C4 (P = 0.0385);

MVP

0.068

MPC

2.0

ClinPred

0.056

GERP RS

0.58

gMVP

0.41

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over