Variant 1-61081983-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 3P and 10B. PM1PP2BP4_StrongBP6_ModerateBS2

The NM_001145512.2(NFIA):c.40G>A(p.Val14Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,550,616 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

NFIA
NM_001145512.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM1

In a DNA_binding_region CTF/NF-I (size 193) in uniprot entity NFIA_HUMAN there are 9 pathogenic changes around while only 3 benign (75%) in NM_001145512.2

PP2

Missense variant where missense usually causes diseases, NFIA

BP4

Computational evidence support a benign effect (MetaRNN=0.011673689).

BP6

Variant 1-61081983-G-A is Benign according to our data. Variant chr1-61081983-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3030877.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIA	NM_001145512.2 linkuse as main transcript	c.40G>A	p.Val14Met	missense_variant	1/12
NFIA	NM_001145511.2 linkuse as main transcript	c.3+4355G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
NFIA	ENST00000371189.8 linkuse as main transcript	c.40G>A	p.Val14Met	missense_variant	1/12	2	Q12857-4
NFIA	ENST00000371191.5 linkuse as main transcript	c.97-6166G>A		intron_variant		5
NFIA	ENST00000407417.7 linkuse as main transcript	c.3+4355G>A		intron_variant		2	Q12857-3

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.00

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000464

AC:

AN:

150988

Hom.:

AF XY:

0.0000247

AC XY:

AN XY:

80826

show subpopulations

Gnomad AFR exome

AF:

0.000695

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000207

AC:

AN:

1398404

Hom.:

Cov.:

AF XY:

0.0000188

AC XY:

AN XY:

689762

show subpopulations

Gnomad4 AFR exome

AF:

0.000696

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000862

GnomAD4 genome

AF:

0.000223

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000310

ExAC

AF:

0.0000811

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NFIA-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.67

Cadd

Benign

Dann

Benign

0.94

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.43

M_CAP

Benign

0.029

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.010

REVEL

Benign

0.043

Sift

Uncertain

0.0090

Sift4G

Benign

0.11

Vest4

0.15

MVP

0.24

MPC

1.7

ClinPred

0.039

GERP RS

1.8

gMVP

0.34

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