9-14190288-A-T

Variant names:

• chr9-14190288-A-T
• rs7034162
• NM_001190737.2:c.563-10508T>A

Variant summary

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

The NM_001190737.2(NFIB):​c.563-10508T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,024 control chromosomes in the GnomAD database, including 50,229 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 0.81 (50229 hom., cov: 32)
• Consequence: NFIB NM_001190737.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 9 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):

• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• macrocephaly, acquired, with impaired intellectual development

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

ENSG00000299834 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.888 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIB	NM_001190737.2	MANE Select	c.563-10508T>A		intron	N/A	NP_001177666.1	O00712-5
	NFIB	NM_001369458.1		c.629-10508T>A		intron	N/A	NP_001356387.1
	NFIB	NM_001369459.1		c.629-10508T>A		intron	N/A	NP_001356388.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIB	ENST00000380953.6	TSL:1 MANE Select	c.563-10508T>A		intron	N/A	ENSP00000370340.1	O00712-5
	NFIB	ENST00000380959.7	TSL:1	c.563-10508T>A		intron	N/A	ENSP00000370346.3	O00712-1
	NFIB	ENST00000397581.7	TSL:5	c.563-10508T>A		intron	N/A	ENSP00000380711.2	Q5VW26

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122807 AN: 151906 Hom.: 50193 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.808 AC: 122894 AN: 152024 Hom.: 50229 Cov.: 32 AF XY: 0.810 AC XY: 60207 AN XY: 74308

African (AFR) AF: 0.707 AC: 29279 AN: 41432

American (AMR) AF: 0.815 AC: 12441 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3091 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3142 AN: 5156

South Asian (SAS) AF: 0.911 AC: 4383 AN: 4812

European-Finnish (FIN) AF: 0.873 AC: 9232 AN: 10580

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58494 AN: 67994

Other (OTH) AF: 0.823 AC: 1733 AN: 2106

Alfa AF: 0.838 Hom.: 6707

Bravo AF: 0.797

Asia WGS AF: 0.768 AC: 2659 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.86
DANN	Benign	0.57
PhyloP100		-0.35
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: rs7034162; hg19: chr9-14190287;