chr19-13024383-T-C

Position:

• chr19-13024383-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001365902.3(NFIX):​c.28-638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 680,594 control chromosomes in the GnomAD database, including 3,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2048 hom., cov: 32)
  • Exomes 𝑓: 0.057 (1222 hom.)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.48

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 19-13024383-T-C is Benign according to our data. Variant chr19-13024383-T-C is described in ClinVar as [Benign]. Clinvar id is 677427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIX	NM_001365902.3	c.28-638T>C		intron_variant		ENST00000592199.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIX	ENST00000592199.6	c.28-638T>C		intron_variant		5	NM_001365902.3	P4

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17516 AN: 152108 Hom.: 2033 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0976

GnomAD4 exome AF: 0.0570 AC: 30099 AN: 528368 Hom.: 1222 AF XY: 0.0571 AC XY: 14131 AN XY: 247594

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.0517

Gnomad4 ASJ exome AF: 0.0460

Gnomad4 EAS exome AF: 0.00275

Gnomad4 SAS exome AF: 0.0383

Gnomad4 FIN exome AF: 0.0301

Gnomad4 NFE exome AF: 0.0520

Gnomad4 OTH exome AF: 0.0642

GnomAD4 genome AF: 0.115 AC: 17570 AN: 152226 Hom.: 2048 Cov.: 32 AF XY: 0.110 AC XY: 8213 AN XY: 74436

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.0636

Gnomad4 ASJ AF: 0.0455

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0304

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0514

Gnomad4 OTH AF: 0.0971

Alfa AF: 0.0996 Hom.: 283

Bravo AF: 0.127

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.44
CADD	Benign	18
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73507341; hg19: chr19-13135197;