chr19-13024113-C-CA

Position:

• chr19-13024113-C-CA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001365902.3(NFIX):​c.28-891dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 402,570 control chromosomes in the GnomAD database, including 275 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (267 hom., cov: 28)
  • Exomes 𝑓: 0.22 (8 hom.)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.632

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 -16 ACMG points.

• BP6: Variant 19-13024113-C-CA is Benign according to our data. Variant chr19-13024113-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 803527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIX	NM_001365902.3	c.28-891dup		intron_variant		ENST00000592199.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIX	ENST00000592199.6	c.28-891dup		intron_variant		5	NM_001365902.3	P4

Frequencies

GnomAD3 genomes AF: 0.0602 AC: 6170 AN: 102522 Hom.: 269 Cov.: 28

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00166

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.00670

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0722

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0544

GnomAD4 exome AF: 0.216 AC: 64674 AN: 300042 Hom.: 8 AF XY: 0.216 AC XY: 34852 AN XY: 161520

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.0602 AC: 6174 AN: 102528 Hom.: 267 Cov.: 28 AF XY: 0.0601 AC XY: 2935 AN XY: 48826

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0531

Gnomad4 ASJ AF: 0.00670

Gnomad4 EAS AF: 0.0291

Gnomad4 SAS AF: 0.0320

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.0541

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 01, 2019

- -

Marshall-Smith syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs113861190; hg19: chr19-13134927;