Genetic Variant NFIA:c.1255-7_1255-5dupCCC (chr1-61406543-G-GCCC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001134673.4(NFIA):c.1255-7_1255-5dupCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

NFIA
NM_001134673.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.886

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

brain malformations with or without urinary tract defects
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
chromosome 1p32-p31 deletion syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics

NFIA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134673.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NFIA	NM_001134673.4	MANE Select	c.1255-7_1255-5dupCCC	splice_region intron	N/A	NP_001128145.1	Q12857-1
NFIA	NM_001145512.2		c.1390-7_1390-5dupCCC	splice_region intron	N/A	NP_001138984.1	Q12857-4
NFIA	NM_001145511.2		c.1231-7_1231-5dupCCC	splice_region intron	N/A	NP_001138983.1	Q12857-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NFIA	ENST00000403491.8	TSL:1 MANE Select	c.1255-19_1255-18insCCC	intron	N/A	ENSP00000384523.3	Q12857-1
NFIA	ENST00000371187.7	TSL:1	c.1255-19_1255-18insCCC	intron	N/A	ENSP00000360229.3	Q12857-2
NFIA	ENST00000371189.8	TSL:2	c.1390-19_1390-18insCCC	intron	N/A	ENSP00000360231.3	Q12857-4

Frequencies

GnomAD3 genomes

AF:

0.000282

AC:

AN:

63828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000417

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000459

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000357

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000328

Gnomad OTH

AF:

0.00122

GnomAD4 exome

AF:

0.000177

AC:

144

AN:

813454

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

407128

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000108

AC:

AN:

18550

American (AMR)

AF:

0.000242

AC:

AN:

20700

Ashkenazi Jewish (ASJ)

AF:

0.000291

AC:

AN:

13724

East Asian (EAS)

AF:

0.000151

AC:

AN:

19858

South Asian (SAS)

AF:

0.000209

AC:

AN:

47848

European-Finnish (FIN)

AF:

0.000535

AC:

AN:

33634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3140

European-Non Finnish (NFE)

AF:

0.000152

AC:

AN:

623494

Other (OTH)

AF:

0.000215

AC:

AN:

32506

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.337

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000282

AC:

AN:

63862

Hom.:

Cov.:

AF XY:

0.000302

AC XY:

AN XY:

29842

show subpopulations

African (AFR)

AF:

0.000157

AC:

AN:

19118

American (AMR)

AF:

0.000417

AC:

AN:

4794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1788

East Asian (EAS)

AF:

0.000460

AC:

AN:

2174

South Asian (SAS)

AF:

0.00

AC:

AN:

1358

European-Finnish (FIN)

AF:

0.000357

AC:

AN:

2800

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000328

AC:

AN:

30452

Other (OTH)

AF:

0.00121

AC:

AN:

824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.89

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-61406543-GCCCCCCCC-GCCCCCCCCCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over