NM_001365902.3:c.560-9549G>A

Variant names:

• chr19-13063498-G-A
• rs11085829
• NM_001365902.3:c.560-9549G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365902.3(NFIX):​c.560-9549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 150,372 control chromosomes in the GnomAD database, including 19,844 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (19844 hom., cov: 29)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 10 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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Illumina, Ambry Genetics
• Marshall-Smith syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina, ClinGen, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIX	NM_001365902.3	c.560-9549G>A		intron_variant	Intron 2 of 10	ENST00000592199.6	NP_001352831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIX	ENST00000592199.6	c.560-9549G>A		intron_variant	Intron 2 of 10	5	NM_001365902.3	ENSP00000467512.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72170 AN: 150264 Hom.: 19805 Cov.: 29

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.480 AC: 72253 AN: 150372 Hom.: 19844 Cov.: 29 AF XY: 0.481 AC XY: 35253 AN XY: 73262

African (AFR) AF: 0.743 AC: 30557 AN: 41128

American (AMR) AF: 0.518 AC: 7861 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1302 AN: 3462

East Asian (EAS) AF: 0.600 AC: 3060 AN: 5096

South Asian (SAS) AF: 0.513 AC: 2444 AN: 4766

European-Finnish (FIN) AF: 0.262 AC: 2605 AN: 9944

Middle Eastern (MID) AF: 0.458 AC: 131 AN: 286

European-Non Finnish (NFE) AF: 0.341 AC: 23011 AN: 67508

Other (OTH) AF: 0.458 AC: 959 AN: 2094

Alfa AF: 0.391 Hom.: 20677

Bravo AF: 0.509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.25
DANN	Benign	0.34
PhyloP100		-1.2
Mutation Taster		=6/94	disease causing (long InDel)

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: rs11085829; hg19: chr19-13174312;