19-13024113-CAAAAAAA-CAAAAAA

Variant names:

• chr19-13024113-CA-C
• rs113861190
• NM_001365902.3:c.28-891delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001365902.3(NFIX):​c.28-891delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 405,882 control chromosomes in the GnomAD database, including 112 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (109 hom., cov: 28)
  • Exomes 𝑓: 0.16 (3 hom.)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.632
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-13024113-CA-C is Benign according to our data. Variant chr19-13024113-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1269465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.

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.28-891delA		intron	N/A	NP_001352831.1	Q14938-1
	NFIX	NM_001378404.1		c.3+96delA		intron	N/A	NP_001365333.1	D2DXM9
	NFIX	NM_001440616.1		c.3+96delA		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.28-907delA		intron	N/A	ENSP00000467512.1	Q14938-1
	NFIX	ENST00000587760.5	TSL:1	c.3+80delA		intron	N/A	ENSP00000466389.1	Q14938-6
	NFIX	ENST00000585575.5	TSL:5	c.3+80delA		intron	N/A	ENSP00000468794.1	Q14938-4

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 4719 AN: 102590 Hom.: 109 Cov.: 28

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.0476

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.0258

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0394

GnomAD4 exome AF: 0.156 AC: 47449 AN: 303288 Hom.: 3 AF XY: 0.157 AC XY: 25600 AN XY: 163522

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

African (AFR) AF: 0.175 AC: 1253 AN: 7142

American (AMR) AF: 0.158 AC: 1675 AN: 10594

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 1758 AN: 8680

East Asian (EAS) AF: 0.158 AC: 2746 AN: 17384

South Asian (SAS) AF: 0.139 AC: 4576 AN: 33014

European-Finnish (FIN) AF: 0.155 AC: 2350 AN: 15138

Middle Eastern (MID) AF: 0.175 AC: 215 AN: 1232

European-Non Finnish (NFE) AF: 0.156 AC: 30205 AN: 193742

Other (OTH) AF: 0.163 AC: 2671 AN: 16362

⚠️ 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: 0.0460 AC: 4723 AN: 102594 Hom.: 109 Cov.: 28 AF XY: 0.0473 AC XY: 2314 AN XY: 48872

African (AFR) AF: 0.0897 AC: 2624 AN: 29266

American (AMR) AF: 0.0240 AC: 235 AN: 9776

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 256 AN: 2536

East Asian (EAS) AF: 0.0139 AC: 49 AN: 3534

South Asian (SAS) AF: 0.0481 AC: 149 AN: 3098

European-Finnish (FIN) AF: 0.0223 AC: 111 AN: 4972

Middle Eastern (MID) AF: 0.0172 AC: 3 AN: 174

European-Non Finnish (NFE) AF: 0.0263 AC: 1242 AN: 47282

Other (OTH) AF: 0.0399 AC: 54 AN: 1352

Alfa AF: 0.00381 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63
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;