1-61082814-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001134673.4(NFIA):ā€‹c.23C>Gā€‹(p.Thr8Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000381 in 1,550,480 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 28)
Exomes š‘“: 0.000039 ( 1 hom. )

Consequence

NFIA
NM_001134673.4 missense

Scores

1
3
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.19
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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 3.6197 (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=0.05380228).
BP6
Variant 1-61082814-C-G is Benign according to our data. Variant chr1-61082814-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3197468.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 55 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFIANM_001134673.4 linkuse as main transcriptc.23C>G p.Thr8Ser missense_variant 1/11 ENST00000403491.8 NP_001128145.1
NFIANM_001145512.2 linkuse as main transcriptc.158C>G p.Thr53Ser missense_variant 2/12 NP_001138984.1
NFIANM_005595.5 linkuse as main transcriptc.23C>G p.Thr8Ser missense_variant 1/10 NP_005586.1
NFIANM_001145511.2 linkuse as main transcriptc.3+5186C>G intron_variant NP_001138983.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NFIAENST00000403491.8 linkuse as main transcriptc.23C>G p.Thr8Ser missense_variant 1/111 NM_001134673.4 ENSP00000384523 P1Q12857-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151894
Hom.:
0
Cov.:
28
show subpopulations
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:
0.000832
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000163
AC:
25
AN:
153598
Hom.:
0
AF XY:
0.000210
AC XY:
17
AN XY:
80986
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:
0.00110
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000393
AC:
55
AN:
1398586
Hom.:
1
Cov.:
39
AF XY:
0.0000594
AC XY:
41
AN XY:
689934
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000682
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151894
Hom.:
0
Cov.:
28
AF XY:
0.0000539
AC XY:
4
AN XY:
74176
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000832
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.000149
AC:
12

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsNov 27, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Benign
0.94
DEOGEN2
Benign
0.16
.;T;.;.;.;.
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.093
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.68
T;T;T;T;T;T
M_CAP
Uncertain
0.097
D
MetaRNN
Benign
0.054
T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.55
.;N;N;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-1.1
N;N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.19
T;T;T;T;T;T
Sift4G
Benign
0.44
T;T;T;T;T;T
Polyphen
0.011, 0.023
.;B;B;.;.;.
Vest4
0.44
MutPred
0.49
.;Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);
MVP
0.35
MPC
0.75
ClinPred
0.22
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.068

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

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

Other links and lift over

dbSNP: rs747260684; hg19: chr1-61548486; API