rs1556032

Variant names:

• chr9-14446003-C-T
• rs1556032
• NM_001369458.1:c.96+85944G>A

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+85944G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,972 control chromosomes in the GnomAD database, including 15,715 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 0.43 (15715 hom., cov: 32)
• Consequence: NFIB NM_001369458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIB	NM_001369458.1	c.96+85944G>A		intron_variant	Intron 1 of 11		NP_001356387.1
NFIB	NM_001369459.1	c.96+85944G>A		intron_variant	Intron 1 of 11		NP_001356388.1
NFIB	NM_001369462.1	c.96+85944G>A		intron_variant	Intron 1 of 9		NP_001356391.1
NFIB	NM_001369468.1	c.96+85944G>A		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.417-22597C>T		intron_variant	Intron 3 of 3
NFIB-AS1	ENST00000842090.1	n.226-68C>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65728 AN: 151854 Hom.: 15711 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.433 AC: 65770 AN: 151972 Hom.: 15715 Cov.: 32 AF XY: 0.436 AC XY: 32343 AN XY: 74258

African (AFR) AF: 0.228 AC: 9454 AN: 41466

American (AMR) AF: 0.562 AC: 8573 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1755 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2346 AN: 5160

South Asian (SAS) AF: 0.365 AC: 1759 AN: 4822

European-Finnish (FIN) AF: 0.544 AC: 5729 AN: 10526

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34595 AN: 67960

Other (OTH) AF: 0.443 AC: 938 AN: 2116

Alfa AF: 0.483 Hom.: 62553

Bravo AF: 0.427

Asia WGS AF: 0.443 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.82
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs1556032; hg19: chr9-14446001;