rs17304036

Variant names:

• chr1-60953520-G-A
• rs17304036
• ENST00000438559.5:n.635+802C>T

Variant summary

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

The ENST00000421455.2(NFIA-AS2):​n.1115C>T 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 0.0751 in 152,272 control chromosomes in the GnomAD database, including 563 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 (563 hom., cov: 33)
• Consequence: NFIA-AS2 ENST00000421455.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695
• Publications: 3 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: Ambry Genetics, Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000421455.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA-AS2	NR_110617.2		n.599+802C>T		intron	N/A
	NFIA-AS2	NR_110618.2		n.*218C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA-AS2	ENST00000438559.5	TSL:1	n.635+802C>T		intron	N/A
	NFIA	ENST00000371191.5	TSL:5	c.96+88054G>A		intron	N/A	ENSP00000360233.1	B1AKN8
	NFIA-AS2	ENST00000421455.2	TSL:4	n.1115C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11430 AN: 152154 Hom.: 563 Cov.: 33

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0610

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0751 AC: 11431 AN: 152272 Hom.: 563 Cov.: 33 AF XY: 0.0736 AC XY: 5482 AN XY: 74440

African (AFR) AF: 0.0186 AC: 772 AN: 41550

American (AMR) AF: 0.0610 AC: 934 AN: 15300

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

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5184

South Asian (SAS) AF: 0.116 AC: 557 AN: 4818

European-Finnish (FIN) AF: 0.101 AC: 1074 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7336 AN: 68028

Other (OTH) AF: 0.0758 AC: 160 AN: 2112

Alfa AF: 0.0849 Hom.: 137

Bravo AF: 0.0683

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17304036;

hg19: chr1-61419192;