rs59677118

Variant names:

• chr9-14441679-G-A
• rs59677118
• NM_001369458.1:c.96+90268C>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+90268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 151,896 control chromosomes in the GnomAD database, including 574 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 0.077 (574 hom., cov: 31)
• Consequence: NFIB NM_001369458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIB	NM_001369458.1	c.96+90268C>T		intron_variant	Intron 1 of 11		NP_001356387.1
NFIB	NM_001369459.1	c.96+90268C>T		intron_variant	Intron 1 of 11		NP_001356388.1
NFIB	NM_001369462.1	c.96+90268C>T		intron_variant	Intron 1 of 9		NP_001356391.1
NFIB	NM_001369468.1	c.96+90268C>T		intron_variant	Intron 1 of 8		NP_001356397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIB-AS1	ENST00000659981.1	n.417-26921G>A		intron_variant	Intron 3 of 3
NFIB-AS1	ENST00000842090.1	n.226-4392G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11656 AN: 151778 Hom.: 573 Cov.: 31

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.0730

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0892

Gnomad OTH AF: 0.0667

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

GnomAD4 genome AF: 0.0768 AC: 11665 AN: 151896 Hom.: 574 Cov.: 31 AF XY: 0.0795 AC XY: 5900 AN XY: 74222

African (AFR) AF: 0.0414 AC: 1717 AN: 41466

American (AMR) AF: 0.0458 AC: 700 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3468

East Asian (EAS) AF: 0.0728 AC: 375 AN: 5152

South Asian (SAS) AF: 0.149 AC: 712 AN: 4786

European-Finnish (FIN) AF: 0.160 AC: 1683 AN: 10500

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0892 AC: 6062 AN: 67940

Other (OTH) AF: 0.0670 AC: 141 AN: 2106

Alfa AF: 0.0863 Hom.: 94

Bravo AF: 0.0650

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.73
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs59677118; hg19: chr9-14441677; COSMIC: COSV60334600;