rs2382437

Positions:

• chr9-14139829-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001190737.2(NFIB):​c.925+6860A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,056 control chromosomes in the GnomAD database, including 7,125 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (7125 hom., cov: 32)
• Consequence: NFIB NM_001190737.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

Genes affected

NFIB (HGNC:7785): (nuclear factor I B) Enables DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and transcription regulator inhibitor activity. Involved in brain development; negative regulation of DNA binding activity; and regulation of transcription by RNA polymerase II. Located in fibrillar center and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NFIB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIB	NM_001190737.2	c.925+6860A>G		intron_variant		ENST00000380953.6	NP_001177666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIB	ENST00000380953.6	c.925+6860A>G		intron_variant		1	NM_001190737.2	ENSP00000370340.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41318 AN: 151938 Hom.: 7108 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.272 AC: 41386 AN: 152056 Hom.: 7125 Cov.: 32 AF XY: 0.272 AC XY: 20195 AN XY: 74308

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.275

Alfa AF: 0.194 Hom.: 4574

Bravo AF: 0.292

Asia WGS AF: 0.318 AC: 1105 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.9
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2382437; hg19: chr9-14139828;