19-13023630-CT-C

Variant names:

• chr19-13023630-CT-C
• rs201731717
• NM_001365902.3:c.28-1376delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001365902.3(NFIX):​c.28-1376delT 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
• Publications: 0 publications found

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]

NFIX Gene-Disease associations (from GenCC):

• Malan overgrowth syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, ClinGen, Orphanet
• Marshall-Smith syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1152 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365902.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIX	NM_001365902.3	MANE Select	c.28-1376delT		intron	N/A	NP_001352831.1	Q14938-1
	NFIX	NM_002501.4		c.28-1376delT		intron	N/A	NP_002492.2	Q14938-3
	NFIX	NM_001365982.2		c.28-1376delT		intron	N/A	NP_001352911.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIX	ENST00000592199.6	TSL:5 MANE Select	c.28-1390delT		intron	N/A	ENSP00000467512.1	Q14938-1
	NFIX	ENST00000397661.6	TSL:5	c.28-1390delT		intron	N/A	ENSP00000380781.2	Q14938-3
	NFIX	ENST00000590027.1	TSL:2	c.-114-1390delT		intron	N/A	ENSP00000465616.1	K7EKH0

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

African (AFR) AF: 0.0239 AC: 814 AN: 34098

American (AMR) AF: 0.00389 AC: 50 AN: 12860

Ashkenazi Jewish (ASJ) AF: 0.00226 AC: 7 AN: 3092

East Asian (EAS) AF: 0.00185 AC: 8 AN: 4314

South Asian (SAS) AF: 0.00452 AC: 18 AN: 3982

European-Finnish (FIN) AF: 0.00502 AC: 36 AN: 7174

Middle Eastern (MID) AF: 0.00800 AC: 2 AN: 250

European-Non Finnish (NFE) AF: 0.00347 AC: 209 AN: 60280

Other (OTH) AF: 0.00463 AC: 8 AN: 1726

Alfa AF: 0.00 Hom.: 46

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201731717; hg19: chr19-13134444;