19-13023630-CTTTTTTTTTTT-CTTT

Variant names:

• chr19-13023630-CTTTTTTTT-C
• rs201731717
• NM_001365902.3:c.28-1383_28-1376delTTTTTTTT

Variant summary

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

The NM_001365902.3(NFIX):​c.28-1383_28-1376delTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 128,650 control chromosomes in the GnomAD database, including 723 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (723 hom., cov: 26)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.435
• 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 19-13023630-CTTTTTTTT-C is Benign according to our data. Variant chr19-13023630-CTTTTTTTT-C is described in ClinVar as Benign. ClinVar VariationId is 1283288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 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.28-1383_28-1376delTTTTTTTT		intron	N/A	NP_001352831.1	Q14938-1
	NFIX	NM_002501.4		c.28-1383_28-1376delTTTTTTTT		intron	N/A	NP_002492.2	Q14938-3
	NFIX	NM_001365982.2		c.28-1383_28-1376delTTTTTTTT		intron	N/A	NP_001352911.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIX	ENST00000592199.6	TSL:5 MANE Select	c.28-1390_28-1383delTTTTTTTT		intron	N/A	ENSP00000467512.1	Q14938-1
	NFIX	ENST00000397661.6	TSL:5	c.28-1390_28-1383delTTTTTTTT		intron	N/A	ENSP00000380781.2	Q14938-3
	NFIX	ENST00000590027.1	TSL:2	c.-114-1390_-114-1383delTTTTTTTT		intron	N/A	ENSP00000465616.1	K7EKH0

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 12856 AN: 128638 Hom.: 720 Cov.: 26

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0114

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.0621

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0526

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.0901

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.100 AC: 12864 AN: 128650 Hom.: 723 Cov.: 26 AF XY: 0.0979 AC XY: 6068 AN XY: 61984

African (AFR) AF: 0.0273 AC: 930 AN: 34106

American (AMR) AF: 0.0962 AC: 1237 AN: 12862

Ashkenazi Jewish (ASJ) AF: 0.0621 AC: 192 AN: 3092

East Asian (EAS) AF: 0.0246 AC: 106 AN: 4316

South Asian (SAS) AF: 0.0823 AC: 328 AN: 3986

European-Finnish (FIN) AF: 0.130 AC: 932 AN: 7178

Middle Eastern (MID) AF: 0.0480 AC: 12 AN: 250

European-Non Finnish (NFE) AF: 0.148 AC: 8958 AN: 60338

Other (OTH) AF: 0.0924 AC: 160 AN: 1732

Alfa AF: 0.0387 Hom.: 46

Bravo AF: 0.0802

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		0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs201731717; hg19: chr19-13134444;