chr19-13047969-G-A

Variant names:

• chr19-13047969-G-A
• rs931067
• NM_001365902.3:c.559+22417G>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.559+22417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,074 control chromosomes in the GnomAD database, including 7,157 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 0.29 (7157 hom., cov: 32)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIX	NM_001365902.3	c.559+22417G>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.559+22417G>A		intron_variant	Intron 2 of 10	5	NM_001365902.3	ENSP00000467512.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43763 AN: 151956 Hom.: 7163 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.288 AC: 43767 AN: 152074 Hom.: 7157 Cov.: 32 AF XY: 0.295 AC XY: 21933 AN XY: 74362

African (AFR) AF: 0.182 AC: 7559 AN: 41448

American (AMR) AF: 0.424 AC: 6482 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1145 AN: 3468

East Asian (EAS) AF: 0.602 AC: 3117 AN: 5178

South Asian (SAS) AF: 0.480 AC: 2317 AN: 4824

European-Finnish (FIN) AF: 0.240 AC: 2535 AN: 10570

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19608 AN: 67992

Other (OTH) AF: 0.305 AC: 642 AN: 2108

Alfa AF: 0.297 Hom.: 14706

Bravo AF: 0.295

Asia WGS AF: 0.468 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.68
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs931067; hg19: chr19-13158783;