NM_001190737.2:c.563-3463A>G

Variant names:

• chr9-14183243-T-C
• rs2382446
• NM_001190737.2:c.563-3463A>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.563-3463A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 152,056 control chromosomes in the GnomAD database, including 75,306 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 1.0 (75306 hom., cov: 28)
• Consequence: NFIB NM_001190737.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 1 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)

ENSG00000299834 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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.563-3463A>G		intron	N/A	NP_001177666.1
	NFIB	NM_001369458.1		c.629-3463A>G		intron	N/A	NP_001356387.1
	NFIB	NM_001369459.1		c.629-3463A>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.563-3463A>G		intron	N/A	ENSP00000370340.1
	NFIB	ENST00000380959.7	TSL:1	c.563-3463A>G		intron	N/A	ENSP00000370346.3
	NFIB	ENST00000397581.7	TSL:5	c.563-3463A>G		intron	N/A	ENSP00000380711.2

Frequencies

GnomAD3 genomes AF: 0.995 AC: 151209 AN: 151938 Hom.: 75246 Cov.: 28

Gnomad AFR AF: 0.984

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.995

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

GnomAD4 genome AF: 0.995 AC: 151328 AN: 152056 Hom.: 75306 Cov.: 28 AF XY: 0.995 AC XY: 73972 AN XY: 74320

African (AFR) AF: 0.984 AC: 40818 AN: 41480

American (AMR) AF: 0.997 AC: 15231 AN: 15276

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3470 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5112 AN: 5112

South Asian (SAS) AF: 1.00 AC: 4811 AN: 4812

European-Finnish (FIN) AF: 1.00 AC: 10602 AN: 10602

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67988 AN: 67998

Other (OTH) AF: 0.995 AC: 2092 AN: 2102

Alfa AF: 0.997 Hom.: 8624

Bravo AF: 0.994

Asia WGS AF: 0.999 AC: 3474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.48
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2382446; hg19: chr9-14183242;