19-13023687-A-T

Variant names:

• chr19-13023687-A-T
• rs1058993
• NM_001365902.3:c.28-1334A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001365902.3(NFIX):​c.28-1334A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 145,980 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.029 (71 hom., cov: 27)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.618
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 19-13023687-A-T is Benign according to our data. Variant chr19-13023687-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 673573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0288 (4198/145980) while in subpopulation NFE AF = 0.0367 (2453/66780). AF 95% confidence interval is 0.0355. There are 71 homozygotes in GnomAd4. There are 1915 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4198 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.28-1334A>T		intron	N/A	NP_001352831.1	Q14938-1
	NFIX	NM_002501.4		c.28-1334A>T		intron	N/A	NP_002492.2	Q14938-3
	NFIX	NM_001365982.2		c.28-1334A>T		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.28-1334A>T		intron	N/A	ENSP00000467512.1	Q14938-1
	NFIX	ENST00000397661.6	TSL:5	c.28-1334A>T		intron	N/A	ENSP00000380781.2	Q14938-3
	NFIX	ENST00000590027.1	TSL:2	c.-114-1334A>T		intron	N/A	ENSP00000465616.1	K7EKH0

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4197 AN: 145892 Hom.: 70 Cov.: 27

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.0632

Gnomad AMR AF: 0.0270

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0274

Gnomad SAS AF: 0.00699

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.0885

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0432

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

GnomAD4 genome AF: 0.0288 AC: 4198 AN: 145980 Hom.: 71 Cov.: 27 AF XY: 0.0270 AC XY: 1915 AN XY: 70900

African (AFR) AF: 0.0186 AC: 724 AN: 39024

American (AMR) AF: 0.0270 AC: 398 AN: 14750

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 132 AN: 3416

East Asian (EAS) AF: 0.0272 AC: 131 AN: 4810

South Asian (SAS) AF: 0.00679 AC: 31 AN: 4566

European-Finnish (FIN) AF: 0.0173 AC: 164 AN: 9482

Middle Eastern (MID) AF: 0.0909 AC: 22 AN: 242

European-Non Finnish (NFE) AF: 0.0367 AC: 2453 AN: 66780

Other (OTH) AF: 0.0428 AC: 86 AN: 2008

Alfa AF: 0.0135 Hom.: 6

Bravo AF: 0.0295

Asia WGS AF: 0.0270 AC: 94 AN: 3462

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
BayesDel_noAF	Benign	-0.98
CADD	Benign	9.9
DANN	Benign	0.49
PhyloP100		0.62
PromoterAI		-0.0088	Neutral
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: rs1058993; hg19: chr19-13134501;