rs2382437

Variant names:

• chr9-14139829-T-C
• rs2382437
• NM_001190737.2:c.925+6860A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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 Gene-Disease associations (from GenCC):

• macrocephaly, acquired, with impaired intellectual development

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190737.2. 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_001190737.2	MANE Select	c.925+6860A>G		intron	N/A	NP_001177666.1
	NFIB	NM_001369458.1		c.991+6860A>G		intron	N/A	NP_001356387.1
	NFIB	NM_001369459.1		c.991+6860A>G		intron	N/A	NP_001356388.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIB	ENST00000380953.6	TSL:1 MANE Select	c.925+6860A>G		intron	N/A	ENSP00000370340.1
	NFIB	ENST00000380959.7	TSL:1	c.925+6860A>G		intron	N/A	ENSP00000370346.3
	NFIB	ENST00000543693.5	TSL:1	c.169+6860A>G		intron	N/A	ENSP00000442888.1

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

African (AFR) AF: 0.473 AC: 19604 AN: 41442

American (AMR) AF: 0.307 AC: 4693 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3468

East Asian (EAS) AF: 0.192 AC: 992 AN: 5158

South Asian (SAS) AF: 0.370 AC: 1782 AN: 4812

European-Finnish (FIN) AF: 0.137 AC: 1449 AN: 10598

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11215 AN: 67994

Other (OTH) AF: 0.275 AC: 581 AN: 2112

Alfa AF: 0.201 Hom.: 6743

Bravo AF: 0.292

Asia WGS AF: 0.318 AC: 1105 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.9
DANN	Benign	0.68
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2382437; hg19: chr9-14139828;