rs10961534

Variant names:

• chr9-14470835-A-G
• rs10961534
• ENST00000659981.1:n.2652A>G

Variant summary

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

The ENST00000659981.1(NFIB-AS1):​n.2652A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,154 control chromosomes in the GnomAD database, including 1,757 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 0.14 (1757 hom., cov: 33)
• Consequence: NFIB-AS1 ENST00000659981.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916
• Publications: 9 publications found

Genes affected

NFIB-AS1 (HGNC:56058): (NFIB antisense RNA 1)

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIB	NM_001369458.1	c.96+61112T>C		intron_variant	Intron 1 of 11		NP_001356387.1
NFIB	NM_001369459.1	c.96+61112T>C		intron_variant	Intron 1 of 11		NP_001356388.1
NFIB	NM_001369462.1	c.96+61112T>C		intron_variant	Intron 1 of 9		NP_001356391.1
NFIB	NM_001369468.1	c.96+61112T>C		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.2652A>G		non_coding_transcript_exon_variant	Exon 4 of 4
NFIB-AS1	ENST00000842090.1	n.303-24303A>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21478 AN: 152036 Hom.: 1757 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.141 AC: 21498 AN: 152154 Hom.: 1757 Cov.: 33 AF XY: 0.138 AC XY: 10294 AN XY: 74412

African (AFR) AF: 0.193 AC: 8011 AN: 41486

American (AMR) AF: 0.132 AC: 2025 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1568 AN: 5146

South Asian (SAS) AF: 0.0891 AC: 429 AN: 4814

European-Finnish (FIN) AF: 0.0736 AC: 781 AN: 10616

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7584 AN: 68008

Other (OTH) AF: 0.155 AC: 327 AN: 2110

Alfa AF: 0.124 Hom.: 6233

Bravo AF: 0.151

Asia WGS AF: 0.172 AC: 598 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	0.30
DANN	Benign	0.44
PhyloP100		-0.92

Splicing

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

Other links and lift over

dbSNP: rs10961534; hg19: chr9-14470833;