rs2382470

Variant names:

• chr9-14387818-A-G
• rs2382470
• NM_001369458.1:c.97-80298T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369458.1(NFIB):​c.97-80298T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,092 control chromosomes in the GnomAD database, including 45,731 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 0.77 (45731 hom., cov: 31)
• Consequence: NFIB NM_001369458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIB	NM_001369458.1		c.97-80298T>C		intron	N/A	NP_001356387.1
	NFIB	NM_001369459.1		c.97-80298T>C		intron	N/A	NP_001356388.1
	NFIB	NM_001369462.1		c.97-80298T>C		intron	N/A	NP_001356391.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIB	ENST00000380934.8	TSL:2	c.108+10706T>C		intron	N/A	ENSP00000370321.4
	NFIB	ENST00000638165.1	TSL:5	n.188+10706T>C		intron	N/A
	NFIB-AS1	ENST00000842090.1		n.142-18587A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117693 AN: 151974 Hom.: 45688 Cov.: 31

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.774 AC: 117788 AN: 152092 Hom.: 45731 Cov.: 31 AF XY: 0.774 AC XY: 57544 AN XY: 74340

African (AFR) AF: 0.799 AC: 33127 AN: 41466

American (AMR) AF: 0.770 AC: 11777 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2334 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4018 AN: 5160

South Asian (SAS) AF: 0.736 AC: 3549 AN: 4820

European-Finnish (FIN) AF: 0.773 AC: 8180 AN: 10578

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52233 AN: 67988

Other (OTH) AF: 0.761 AC: 1606 AN: 2110

Alfa AF: 0.764 Hom.: 189739

Bravo AF: 0.773

Asia WGS AF: 0.759 AC: 2640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.96
DANN	Benign	0.35
PhyloP100		0.039
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2382470; hg19: chr9-14387817;