rs1572312

Variant names:

• chr1-60952057-G-T
• rs1572312
• ENST00000438559.5:n.809+454C>A

Variant summary

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

The ENST00000438559.5(NFIA-AS2):​n.809+454C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0966 in 152,236 control chromosomes in the GnomAD database, including 735 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 0.097 (735 hom., cov: 33)
• Consequence: NFIA-AS2 ENST00000438559.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 23 publications found

Genes affected

NFIA-AS2 (HGNC:40401): (NFIA antisense RNA 2)

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIA-AS2	NR_110617.2	n.773+454C>A		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIA-AS2	ENST00000438559.5	n.809+454C>A		intron_variant	Intron 5 of 6	1
NFIA-AS2	ENST00000421455.2	n.2578C>A		non_coding_transcript_exon_variant	Exon 3 of 3	4
NFIA	ENST00000371191.5	c.96+86591G>T		intron_variant	Intron 1 of 10	5		ENSP00000360233.1

Frequencies

GnomAD3 genomes AF: 0.0966 AC: 14696 AN: 152116 Hom.: 735 Cov.: 33

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0912

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

GnomAD4 genome AF: 0.0966 AC: 14708 AN: 152236 Hom.: 735 Cov.: 33 AF XY: 0.0949 AC XY: 7063 AN XY: 74432

African (AFR) AF: 0.0891 AC: 3702 AN: 41546

American (AMR) AF: 0.0705 AC: 1079 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3472

East Asian (EAS) AF: 0.0309 AC: 160 AN: 5186

South Asian (SAS) AF: 0.137 AC: 659 AN: 4806

European-Finnish (FIN) AF: 0.101 AC: 1072 AN: 10598

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7341 AN: 68006

Other (OTH) AF: 0.0917 AC: 194 AN: 2116

Alfa AF: 0.101 Hom.: 2607

Bravo AF: 0.0926

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.056
DANN	Benign	0.59
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1572312; hg19: chr1-61417729;