9-14429309-T-C

Variant names:

• chr9-14429309-T-C
• rs4741377
• NM_001369458.1:c.96+102638A>G

Variant summary

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

The NM_001369458.1(NFIB):​c.96+102638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,958 control chromosomes in the GnomAD database, including 12,619 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 0.40 (12619 hom., cov: 32)
• Consequence: NFIB NM_001369458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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]

ENSG00000287708 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIB	NM_001369458.1	c.96+102638A>G		intron_variant	Intron 1 of 11		NP_001356387.1
NFIB	NM_001369459.1	c.96+102638A>G		intron_variant	Intron 1 of 11		NP_001356388.1
NFIB	NM_001369462.1	c.96+102638A>G		intron_variant	Intron 1 of 9		NP_001356391.1
NFIB	NM_001369468.1	c.96+102638A>G		intron_variant	Intron 1 of 8		NP_001356397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287708	ENST00000659981.1	n.416+22821T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60844 AN: 151840 Hom.: 12604 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.401 AC: 60906 AN: 151958 Hom.: 12619 Cov.: 32 AF XY: 0.403 AC XY: 29959 AN XY: 74272

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.415

Alfa AF: 0.412 Hom.: 13496

Bravo AF: 0.407

Asia WGS AF: 0.370 AC: 1286 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4741377; hg19: chr9-14429307;