9-14149281-T-G

Variant names:

• chr9-14149281-T-G
• rs10511592
• NM_001190737.2:c.806+864A>C

Variant summary

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

The NM_001190737.2(NFIB):​c.806+864A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,120 control chromosomes in the GnomAD database, including 2,948 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 0.19 (2948 hom., cov: 32)
• Consequence: NFIB NM_001190737.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 2 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

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 = 0.344 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.806+864A>C		intron	N/A	NP_001177666.1	O00712-5
	NFIB	NM_001369458.1		c.872+864A>C		intron	N/A	NP_001356387.1
	NFIB	NM_001369459.1		c.872+864A>C		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.806+864A>C		intron	N/A	ENSP00000370340.1	O00712-5
	NFIB	ENST00000380959.7	TSL:1	c.806+864A>C		intron	N/A	ENSP00000370346.3	O00712-1
	NFIB	ENST00000543693.5	TSL:1	c.50+864A>C		intron	N/A	ENSP00000442888.1	O00712-6

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28429 AN: 152002 Hom.: 2948 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.187 AC: 28443 AN: 152120 Hom.: 2948 Cov.: 32 AF XY: 0.191 AC XY: 14233 AN XY: 74358

African (AFR) AF: 0.194 AC: 8038 AN: 41504

American (AMR) AF: 0.269 AC: 4112 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 782 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1395 AN: 5176

South Asian (SAS) AF: 0.359 AC: 1728 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1572 AN: 10592

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10179 AN: 67986

Other (OTH) AF: 0.205 AC: 431 AN: 2106

Alfa AF: 0.159 Hom.: 267

Bravo AF: 0.195

Asia WGS AF: 0.342 AC: 1178 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.46
PhyloP100		0.058
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: rs10511592; hg19: chr9-14149280;