Genetic Variant NFIA:c.1255-9_1255-8insG (chr1-61406553-C-CG) – 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_1255-8insG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,319,428 control chromosomes in the GnomAD database, including 2 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 0.000083 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00011 ( 2 hom. )

Consequence

NFIA
NM_001134673.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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-CG is Benign according to our data. Variant chr1-61406553-C-CG is described in ClinVar as [Likely_benign]. Clinvar id is 1567142.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001134673.4 link	c.1255-9_1255-8insG	splice_region_variant, intron_variant	Intron 8 of 10	ENST00000403491.8	NP_001128145.1	Q12857-1
NFIA	NM_001145512.2 link	c.1390-9_1390-8insG	splice_region_variant, intron_variant	Intron 9 of 11		NP_001138984.1	Q12857-4
NFIA	NM_001145511.2 link	c.1231-9_1231-8insG	splice_region_variant, intron_variant	Intron 8 of 10		NP_001138983.1	Q12857-3
NFIA	NM_005595.5 link	c.1255-9_1255-8insG	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_1255-8insG		splice_region_variant, intron_variant	Intron 8 of 10	1	NM_001134673.4	ENSP00000384523.3		Q12857-1

Frequencies

GnomAD3 genomes

AF:

0.0000827

AC:

AN:

120848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000891

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000326

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000336

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000374

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000370

AC:

AN:

140716

Hom.:

AF XY:

0.000297

AC XY:

AN XY:

77414

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000131

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000503

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000110

AC:

132

AN:

1198490

Hom.:

Cov.:

AF XY:

0.0000923

AC XY:

AN XY:

595804

show subpopulations

Gnomad4 AFR exome

AF:

0.0000740

Gnomad4 AMR exome

AF:

0.00155

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000370

Gnomad4 SAS exome

AF:

0.000102

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000733

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.0000827

AC:

AN:

120938

Hom.:

Cov.:

AF XY:

0.0000677

AC XY:

AN XY:

59104

show subpopulations

Gnomad4 AFR

AF:

0.0000889

Gnomad4 AMR

AF:

0.000325

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000336

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 10, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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