Genetic Variant NFIX:c.28-895_28-891delAAAAA (chr19-13024113-CAAAAA-C) – 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_001365902.3(NFIX):c.28-895_28-891delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 412,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000058 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

NFIX
NM_001365902.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

Publications

0 publications found

Variant links:

Genes affected

NFIX (HGNC:7788): (nuclear factor I X) The protein encoded by this gene is a transcription factor that binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3 in viral and cellular promoters. The encoded protein can also stimulate adenovirus replication in vitro. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

NFIX Gene-Disease associations (from GenCC):

Malan overgrowth syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, ClinGen, Orphanet
Marshall-Smith syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

NFIX links:

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ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365902.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NFIX	NM_001365902.3	MANE Select	c.28-895_28-891delAAAAA	intron	N/A	NP_001352831.1	Q14938-1
NFIX	NM_001378404.1		c.3+92_3+96delAAAAA	intron	N/A	NP_001365333.1	D2DXM9
NFIX	NM_001440616.1		c.3+92_3+96delAAAAA	intron	N/A	NP_001427545.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NFIX	ENST00000592199.6	TSL:5 MANE Select	c.28-907_28-903delAAAAA	intron	N/A	ENSP00000467512.1	Q14938-1
NFIX	ENST00000587760.5	TSL:1	c.3+80_3+84delAAAAA	intron	N/A	ENSP00000466389.1	Q14938-6
NFIX	ENST00000585575.5	TSL:5	c.3+80_3+84delAAAAA	intron	N/A	ENSP00000468794.1	Q14938-4

Frequencies

GnomAD3 genomes

AF:

0.0000584

AC:

AN:

102670

Hom.:

Cov.:

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:

0.00169

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000316

AC:

AN:

309740

Hom.:

AF XY:

0.000264

AC XY:

AN XY:

166960

show subpopulations

African (AFR)

AF:

0.000138

AC:

AN:

7262

American (AMR)

AF:

0.000185

AC:

AN:

10798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8846

East Asian (EAS)

AF:

0.00398

AC:

AN:

17838

South Asian (SAS)

AF:

0.000148

AC:

AN:

33800

European-Finnish (FIN)

AF:

0.000260

AC:

AN:

15366

Middle Eastern (MID)

AF:

0.000794

AC:

AN:

1260

European-Non Finnish (NFE)

AF:

0.0000657

AC:

AN:

197862

Other (OTH)

AF:

0.0000599

AC:

AN:

16708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.0000584

AC:

AN:

102676

Hom.:

Cov.:

AF XY:

0.0000818

AC XY:

AN XY:

48914

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29290

American (AMR)

AF:

0.00

AC:

AN:

9782

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2542

East Asian (EAS)

AF:

0.00170

AC:

AN:

3538

South Asian (SAS)

AF:

0.00

AC:

AN:

3098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

47326

Other (OTH)

AF:

0.00

AC:

AN:

1352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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.:

Bravo

AF:

0.0000604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Splicing

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

Publications

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19-13024113-CAAAAAAA-CAA

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