19-13023687-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001365902.3(NFIX):c.28-1334A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 145,980 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.029 (71 hom., cov: 27)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.618

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 19-13023687-A-T is Benign according to our data. Variant chr19-13023687-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 673573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0288 (4198/145980) while in subpopulation NFE AF= 0.0367 (2453/66780). AF 95% confidence interval is 0.0355. There are 71 homozygotes in gnomad4. There are 1915 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd at 4197 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIX	NM_001365902.3	c.28-1334A>T		intron_variant		ENST00000592199.6
NFIX	NM_001365982.2	c.28-1334A>T		intron_variant
NFIX	NM_002501.4	c.28-1334A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIX	ENST00000592199.6	c.28-1334A>T		intron_variant		5	NM_001365902.3	P4
NFIX	ENST00000397661.6	c.28-1334A>T		intron_variant		5
NFIX	ENST00000590027.1	c.-114-1334A>T		intron_variant		2
NFIX	ENST00000585382.5	c.-114-1334A>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4197 AN: 145892 Hom.: 70 Cov.: 27

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.0632

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0274

Gnomad SAS AF: 0.00699

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.0885

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0432

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

GnomAD4 genome AF: 0.0288 AC: 4198 AN: 145980 Hom.: 71 Cov.: 27 AF XY: 0.0270 AC XY: 1915 AN XY: 70900

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.0270

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.00679

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0367

Gnomad4 OTH AF: 0.0428

Alfa AF: 0.0135 Hom.: 6

Bravo AF: 0.0295

Asia WGS AF: 0.0270 AC: 94 AN: 3462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	9.9
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs1058993; hg19: chr19-13134501;