rs10435726

Variant names:

• chr9-14251918-G-T
• rs10435726
• NM_001190737.2:c.562+55071C>A

Variant summary

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

The NM_001190737.2(NFIB):​c.562+55071C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 152,256 control chromosomes in the GnomAD database, including 604 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 0.075 (604 hom., cov: 33)
• Consequence: NFIB NM_001190737.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 1 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 Gene-Disease associations (from GenCC):

• macrocephaly, acquired, with impaired intellectual development

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIB	NM_001190737.2	c.562+55071C>A		intron_variant	Intron 2 of 10	ENST00000380953.6	NP_001177666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIB	ENST00000380953.6	c.562+55071C>A		intron_variant	Intron 2 of 10	1	NM_001190737.2	ENSP00000370340.1

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11393 AN: 152136 Hom.: 604 Cov.: 33

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0394

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0550

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

GnomAD4 genome AF: 0.0748 AC: 11394 AN: 152256 Hom.: 604 Cov.: 33 AF XY: 0.0749 AC XY: 5577 AN XY: 74442

African (AFR) AF: 0.0179 AC: 744 AN: 41548

American (AMR) AF: 0.0394 AC: 602 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.125 AC: 651 AN: 5188

South Asian (SAS) AF: 0.0888 AC: 428 AN: 4818

European-Finnish (FIN) AF: 0.150 AC: 1586 AN: 10600

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7125 AN: 68012

Other (OTH) AF: 0.0544 AC: 115 AN: 2114

Alfa AF: 0.0882 Hom.: 1382

Bravo AF: 0.0615

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.51
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10435726; hg19: chr9-14251917;