19-13023630-CT-C

Position:

• chr19-13023630-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001365902.3(NFIX):​c.28-1376del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00896 in 128,566 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0090 (6 hom., cov: 26)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.607

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 -10 ACMG points.

• BP6: Variant 19-13023630-CT-C is Benign according to our data. Variant chr19-13023630-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1203397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00896 (1152/128566) while in subpopulation AFR AF= 0.0239 (814/34098). AF 95% confidence interval is 0.0225. There are 6 homozygotes in gnomad4. There are 573 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1152 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIX	NM_001365902.3	c.28-1376del		intron_variant		ENST00000592199.6
NFIX	NM_001365982.2	c.28-1376del		intron_variant
NFIX	NM_002501.4	c.28-1376del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIX	ENST00000592199.6	c.28-1376del		intron_variant		5	NM_001365902.3	P4
NFIX	ENST00000397661.6	c.28-1376del		intron_variant		5
NFIX	ENST00000590027.1	c.-114-1376del		intron_variant		2
NFIX	ENST00000585382.5	c.-114-1376del		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00895 AC: 1150 AN: 128556 Hom.: 6 Cov.: 26

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00389

Gnomad ASJ AF: 0.00226

Gnomad EAS AF: 0.00185

Gnomad SAS AF: 0.00450

Gnomad FIN AF: 0.00502

Gnomad MID AF: 0.00752

Gnomad NFE AF: 0.00347

Gnomad OTH AF: 0.00467

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

GnomAD4 genome AF: 0.00896 AC: 1152 AN: 128566 Hom.: 6 Cov.: 26 AF XY: 0.00925 AC XY: 573 AN XY: 61930

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.00389

Gnomad4 ASJ AF: 0.00226

Gnomad4 EAS AF: 0.00185

Gnomad4 SAS AF: 0.00452

Gnomad4 FIN AF: 0.00502

Gnomad4 NFE AF: 0.00347

Gnomad4 OTH AF: 0.00463

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

Aug 20, 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: rs201731717; hg19: chr19-13134444;