rs1008943

Positions:

• chr9-14434740-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369458.1(NFIB):​c.96+97207A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,138 control chromosomes in the GnomAD database, including 9,464 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 0.34 (9464 hom., cov: 33)
• Consequence: NFIB NM_001369458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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]

ENSG00000287708 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIB	NM_001369458.1	c.96+97207A>T		intron_variant			NP_001356387.1
NFIB	NM_001369459.1	c.96+97207A>T		intron_variant			NP_001356388.1
NFIB	NM_001369462.1	c.96+97207A>T		intron_variant			NP_001356391.1
NFIB	NM_001369468.1	c.96+97207A>T		intron_variant			NP_001356397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000287708	ENST00000659981.1	n.416+28252T>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51921 AN: 152020 Hom.: 9452 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.342 AC: 51968 AN: 152138 Hom.: 9464 Cov.: 33 AF XY: 0.346 AC XY: 25746 AN XY: 74374

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.354

Alfa AF: 0.342 Hom.: 1134

Bravo AF: 0.341

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.44
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1008943; hg19: chr9-14434738;