rs990937

Variant names:

• chr9-14427729-G-A
• rs990937
• NM_001369458.1:c.96+104218C>T

Variant summary

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

The NM_001369458.1(NFIB):​c.96+104218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 152,112 control chromosomes in the GnomAD database, including 147 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 0.037 (147 hom., cov: 32)
• Consequence: NFIB NM_001369458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623
• 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-AS1 (HGNC:56058): (NFIB antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369458.1. 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_001369458.1		c.96+104218C>T		intron	N/A	NP_001356387.1
	NFIB	NM_001369459.1		c.96+104218C>T		intron	N/A	NP_001356388.1
	NFIB	NM_001369462.1		c.96+104218C>T		intron	N/A	NP_001356391.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIB-AS1	ENST00000659981.1		n.416+21241G>A		intron	N/A
	NFIB-AS1	ENST00000842090.1		n.226-18342G>A		intron	N/A
	NFIB-AS1	ENST00000842091.1		n.482-2344G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5667 AN: 151994 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0212

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.0425

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0372 AC: 5663 AN: 152112 Hom.: 147 Cov.: 32 AF XY: 0.0384 AC XY: 2853 AN XY: 74362

African (AFR) AF: 0.0618 AC: 2563 AN: 41482

American (AMR) AF: 0.0212 AC: 323 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3470

East Asian (EAS) AF: 0.0654 AC: 338 AN: 5168

South Asian (SAS) AF: 0.0424 AC: 204 AN: 4814

European-Finnish (FIN) AF: 0.0362 AC: 383 AN: 10590

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0231 AC: 1568 AN: 68000

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0281 Hom.: 105

Bravo AF: 0.0375

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.63
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs990937; hg19: chr9-14427727;