9-14149281-T-G

Position:

• chr9-14149281-T-G

Variant summary

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

The NM_001190737.2(NFIB):​c.806+864A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,120 control chromosomes in the GnomAD database, including 2,948 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 0.19 (2948 hom., cov: 32)
• Consequence: NFIB NM_001190737.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIB	NM_001190737.2	c.806+864A>C		intron_variant		ENST00000380953.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIB	ENST00000380953.6	c.806+864A>C		intron_variant		1	NM_001190737.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28429 AN: 152002 Hom.: 2948 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.187 AC: 28443 AN: 152120 Hom.: 2948 Cov.: 32 AF XY: 0.191 AC XY: 14233 AN XY: 74358

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.205

Alfa AF: 0.157 Hom.: 254

Bravo AF: 0.195

Asia WGS AF: 0.342 AC: 1178 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.46

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: rs10511592; hg19: chr9-14149280;