19-12995977-C-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.27+113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 334,074 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (69 hom., cov: 29)
  • Exomes 𝑓: 0.035 (116 hom.)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.600

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=-0.83).
• BP6: Variant 19-12995977-C-T is Benign according to our data. Variant chr19-12995977-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 677498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0276 (4095/148622) while in subpopulation NFE AF= 0.0362 (2416/66832). AF 95% confidence interval is 0.0349. There are 69 homozygotes in gnomad4. There are 1882 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd at 4096 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIX	NM_001365902.3	c.27+113C>T		intron_variant		ENST00000592199.6
NFIX	NM_001365982.2	c.27+113C>T		intron_variant
NFIX	NM_002501.4	c.27+113C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIX	ENST00000592199.6	c.27+113C>T		intron_variant		5	NM_001365902.3	P4
NFIX	ENST00000397661.6	c.27+113C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4096 AN: 148512 Hom.: 69 Cov.: 29

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0611

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0396

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00794

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.0839

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0416

GnomAD4 exome AF: 0.0350 AC: 6486 AN: 185452 Hom.: 116 AF XY: 0.0358 AC XY: 3155 AN XY: 88214

Gnomad4 AFR exome AF: 0.0202

Gnomad4 AMR exome AF: 0.0169

Gnomad4 ASJ exome AF: 0.0439

Gnomad4 EAS exome AF: 0.00132

Gnomad4 SAS exome AF: 0.00789

Gnomad4 FIN exome AF: 0.0196

Gnomad4 NFE exome AF: 0.0359

Gnomad4 OTH exome AF: 0.0367

GnomAD4 genome AF: 0.0276 AC: 4095 AN: 148622 Hom.: 69 Cov.: 29 AF XY: 0.0259 AC XY: 1882 AN XY: 72548

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.0295

Gnomad4 ASJ AF: 0.0396

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.00794

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0411

Alfa AF: 0.0293 Hom.: 9

Bravo AF: 0.0289

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	-0.83
Cadd	Benign	15
Dann	Benign	0.96
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4

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: rs189556314; hg19: chr19-13106791;