chr1-61079500-A-G

Variant names:

• chr1-61079500-A-G
• rs12130085
• ENST00000371191.5:c.97-8649A>G

Variant summary

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

The ENST00000371191.5(NFIA):​c.97-8649A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,278 control chromosomes in the GnomAD database, including 612 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 0.084 (612 hom., cov: 33)
• Consequence: NFIA ENST00000371191.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 2 publications found

Genes affected

NFIA (HGNC:7784): (nuclear factor I A) This gene encodes a member of the NF1 (nuclear factor 1) family of transcription factors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

NFIA Gene-Disease associations (from GenCC):

• brain malformations with or without urinary tract defects

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• chromosome 1p32-p31 deletion syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001145511.2	c.3+1872A>G		intron_variant	Intron 1 of 10		NP_001138983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000371191.5	c.97-8649A>G		intron_variant	Intron 1 of 10	5		ENSP00000360233.1
NFIA	ENST00000407417.7	c.3+1872A>G		intron_variant	Intron 1 of 10	2		ENSP00000384680.2
NFIA	ENST00000699964.1	c.3+1872A>G		intron_variant	Intron 1 of 9			ENSP00000514720.1

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12835 AN: 152160 Hom.: 605 Cov.: 33

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0852

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

GnomAD4 genome AF: 0.0844 AC: 12855 AN: 152278 Hom.: 612 Cov.: 33 AF XY: 0.0834 AC XY: 6210 AN XY: 74458

African (AFR) AF: 0.0560 AC: 2329 AN: 41562

American (AMR) AF: 0.0857 AC: 1310 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 214 AN: 3472

East Asian (EAS) AF: 0.104 AC: 537 AN: 5182

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4826

European-Finnish (FIN) AF: 0.0702 AC: 745 AN: 10612

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

European-Non Finnish (NFE) AF: 0.104 AC: 7099 AN: 68018

Other (OTH) AF: 0.0919 AC: 194 AN: 2110

Alfa AF: 0.0956 Hom.: 358

Bravo AF: 0.0826

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.84
PhyloP100		2.6
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12130085; hg19: chr1-61545172;