9-14429309-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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-AS1 (HGNC:56058): (NFIB antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369458.1. 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
	NFIB	NM_001369458.1		c.96+102638A>G		intron	N/A	NP_001356387.1
	NFIB	NM_001369459.1		c.96+102638A>G		intron	N/A	NP_001356388.1
	NFIB	NM_001369462.1		c.96+102638A>G		intron	N/A	NP_001356391.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIB-AS1	ENST00000659981.1		n.416+22821T>C		intron	N/A
	NFIB-AS1	ENST00000842090.1		n.226-16762T>C		intron	N/A
	NFIB-AS1	ENST00000842091.1		n.482-764T>C		intron	N/A

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

African (AFR) AF: 0.326 AC: 13511 AN: 41440

American (AMR) AF: 0.535 AC: 8169 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2050 AN: 5152

South Asian (SAS) AF: 0.301 AC: 1451 AN: 4820

European-Finnish (FIN) AF: 0.467 AC: 4933 AN: 10554

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28219 AN: 67938

Other (OTH) AF: 0.415 AC: 876 AN: 2110

Alfa AF: 0.413 Hom.: 17584

Bravo AF: 0.407

Asia WGS AF: 0.370 AC: 1286 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.49
PhyloP100		-0.0050

Splicing

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

Other links and lift over

dbSNP: rs4741377; hg19: chr9-14429307;