19-13024520-G-C

Position:

• chr19-13024520-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001365902.3(NFIX):​c.28-501G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,515,198 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (19 hom.)
• Consequence: NFIX NM_001365902.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.450

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-13024520-G-C is Benign according to our data. Variant chr19-13024520-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1675724.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 280 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIX	NM_001365902.3	c.28-501G>C		intron_variant		ENST00000592199.6	NP_001352831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIX	ENST00000592199.6	c.28-501G>C		intron_variant		5	NM_001365902.3	ENSP00000467512.1

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 281 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.00328 AC: 4470 AN: 1362856 Hom.: 19 Cov.: 32 AF XY: 0.00341 AC XY: 2284 AN XY: 669320

Gnomad4 AFR exome AF: 0.000485

Gnomad4 AMR exome AF: 0.000472

Gnomad4 ASJ exome AF: 0.00753

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00629

Gnomad4 FIN exome AF: 0.0000598

Gnomad4 NFE exome AF: 0.00332

Gnomad4 OTH exome AF: 0.00383

GnomAD4 genome AF: 0.00184 AC: 280 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.00156 AC XY: 116 AN XY: 74506

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00287

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000372 Hom.: 0

Bravo AF: 0.00160

Asia WGS AF: 0.00231 AC: 8 AN: 3478

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

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

NFIX: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.81

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: rs185692550; hg19: chr19-13135334;