9-14088120-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001190737.2(NFIB):c.*189A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,281,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: NFIB NM_001190737.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.10

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP6: Variant 9-14088120-T-A is Benign according to our data. Variant chr9-14088120-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2659074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 150 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIB	NM_001190737.2	c.*189A>T		3_prime_UTR_variant	11/11	ENST00000380953.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIB	ENST00000380953.6	c.*189A>T		3_prime_UTR_variant	11/11	1	NM_001190737.2

Frequencies

GnomAD3 genomes AF: 0.000986 AC: 150 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.00113 AC: 1279 AN: 1128868 Hom.: 0 Cov.: 15 AF XY: 0.00113 AC XY: 623 AN XY: 549246

Gnomad4 AFR exome AF: 0.000203

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000316

Gnomad4 FIN exome AF: 0.00190

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.000985 AC: 150 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74454

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00148

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00138 Hom.: 0

Bravo AF: 0.000971

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

NFIB: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
Cadd	Benign	16
Dann	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs548618850; hg19: chr9-14088119;