19-13024113-CAAAAAAA-CAAAAA

Variant names:

• chr19-13024113-CAA-C
• rs113861190
• NM_001365902.3:c.28-892_28-891delAA

Variant summary

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

The NM_001365902.3(NFIX):​c.28-892_28-891delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 404,852 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 0.0011 (0 hom., cov: 28)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 0 publications found

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

ACMG classification

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

• BS2: High AC in GnomAd4 at 108 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIX	NM_001365902.3	MANE Select	c.28-892_28-891delAA		intron	N/A	NP_001352831.1	Q14938-1
	NFIX	NM_001378404.1		c.3+95_3+96delAA		intron	N/A	NP_001365333.1	D2DXM9
	NFIX	NM_001440616.1		c.3+95_3+96delAA		intron	N/A	NP_001427545.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIX	ENST00000592199.6	TSL:5 MANE Select	c.28-907_28-906delAA		intron	N/A	ENSP00000467512.1	Q14938-1
	NFIX	ENST00000587760.5	TSL:1	c.3+80_3+81delAA		intron	N/A	ENSP00000466389.1	Q14938-6
	NFIX	ENST00000585575.5	TSL:5	c.3+80_3+81delAA		intron	N/A	ENSP00000468794.1	Q14938-4

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 107 AN: 102646 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000511

Gnomad ASJ AF: 0.000393

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000201

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000275

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0204 AC: 6155 AN: 302200 Hom.: 0 AF XY: 0.0206 AC XY: 3359 AN XY: 162914

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

African (AFR) AF: 0.0246 AC: 175 AN: 7116

American (AMR) AF: 0.0242 AC: 255 AN: 10548

Ashkenazi Jewish (ASJ) AF: 0.0240 AC: 207 AN: 8622

East Asian (EAS) AF: 0.0205 AC: 354 AN: 17310

South Asian (SAS) AF: 0.0194 AC: 639 AN: 33000

European-Finnish (FIN) AF: 0.0209 AC: 314 AN: 14990

Middle Eastern (MID) AF: 0.0197 AC: 24 AN: 1220

European-Non Finnish (NFE) AF: 0.0199 AC: 3835 AN: 193134

Other (OTH) AF: 0.0216 AC: 352 AN: 16260

⚠️ 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.

GnomAD4 genome AF: 0.00105 AC: 108 AN: 102652 Hom.: 0 Cov.: 28 AF XY: 0.00119 AC XY: 58 AN XY: 48896

African (AFR) AF: 0.00297 AC: 87 AN: 29286

American (AMR) AF: 0.000511 AC: 5 AN: 9782

Ashkenazi Jewish (ASJ) AF: 0.000393 AC: 1 AN: 2542

East Asian (EAS) AF: 0.000283 AC: 1 AN: 3538

South Asian (SAS) AF: 0.00 AC: 0 AN: 3098

European-Finnish (FIN) AF: 0.000201 AC: 1 AN: 4968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 174

European-Non Finnish (NFE) AF: 0.000275 AC: 13 AN: 47308

Other (OTH) AF: 0.00 AC: 0 AN: 1352

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs113861190; hg19: chr19-13134927;