dbSNP rs777624713: NFIA:c.1255-9_1255-8insA (chr1-61406553-C-CA) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001134673.4(NFIA):c.1255-9_1255-8insA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,198,484 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00013 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

NFIA
NM_001134673.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.165

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-61406553-C-CA is Benign according to our data. Variant chr1-61406553-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 435979.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001134673.4 link	c.1255-9_1255-8insA	splice_region_variant, intron_variant	Intron 8 of 10	ENST00000403491.8	NP_001128145.1	Q12857-1
NFIA	NM_001145512.2 link	c.1390-9_1390-8insA	splice_region_variant, intron_variant	Intron 9 of 11		NP_001138984.1	Q12857-4
NFIA	NM_001145511.2 link	c.1231-9_1231-8insA	splice_region_variant, intron_variant	Intron 8 of 10		NP_001138983.1	Q12857-3
NFIA	NM_005595.5 link	c.1255-9_1255-8insA	splice_region_variant, intron_variant	Intron 8 of 9		NP_005586.1	Q12857-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8 link	c.1255-9_1255-8insA		splice_region_variant, intron_variant	Intron 8 of 10	1	NM_001134673.4	ENSP00000384523.3		Q12857-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

120848

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000594

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000524

Gnomad OTH

AF:

0.000654

GnomAD3 exomes

AF:

0.0000853

AC:

AN:

140716

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

77414

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:

0.0000585

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.000638

GnomAD4 exome

AF:

0.000132

AC:

158

AN:

1198484

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

595798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000370

Gnomad4 SAS exome

AF:

0.0000146

Gnomad4 FIN exome

AF:

0.0000233

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.000208

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000256

AC:

AN:

120938

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

AN XY:

59104

show subpopulations

Gnomad4 AFR

AF:

0.0000592

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000524

Gnomad4 OTH

AF:

0.000648

Alfa

AF:

0.0000966

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 15, 2017

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

NFIA-related disorder

Benign:1

May 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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

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