dbSNP rs58081092: NFIA:c.1255-12_1255-5delCCCCCCCC (chr1-61406543-GCCCCCCCC-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001134673.4(NFIA):c.1255-12_1255-5delCCCCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000086 in 813,518 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

NFIA
NM_001134673.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001134673.4 link	c.1255-12_1255-5delCCCCCCCC	splice_region_variant, intron_variant	Intron 8 of 10	ENST00000403491.8	NP_001128145.1	Q12857-1
NFIA	NM_001145512.2 link	c.1390-12_1390-5delCCCCCCCC	splice_region_variant, intron_variant	Intron 9 of 11		NP_001138984.1	Q12857-4
NFIA	NM_001145511.2 link	c.1231-12_1231-5delCCCCCCCC	splice_region_variant, intron_variant	Intron 8 of 10		NP_001138983.1	Q12857-3
NFIA	NM_005595.5 link	c.1255-12_1255-5delCCCCCCCC	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.1255-18_1255-11delCCCCCCCC		intron_variant	Intron 8 of 10	1	NM_001134673.4	ENSP00000384523.3		Q12857-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000860

AC:

AN:

813518

Hom.:

AF XY:

0.00000982

AC XY:

AN XY:

407166

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

18556

American (AMR)

AF:

0.00

AC:

AN:

20702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13726

East Asian (EAS)

AF:

0.00

AC:

AN:

19860

South Asian (SAS)

AF:

0.00

AC:

AN:

47852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33636

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3142

European-Non Finnish (NFE)

AF:

0.0000112

AC:

AN:

623536

Other (OTH)

AF:

0.00

AC:

AN:

32508

⚠️ 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: 0.232

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over