1-60890848-G-T

Variant names:

• chr1-60890848-G-T
• rs12122228
• ENST00000371191.5:c.96+25382G>T

Variant summary

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

The ENST00000664495.1(NFIA):​n.96+25382G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,188 control chromosomes in the GnomAD database, including 960 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 0.11 (960 hom., cov: 32)
• Consequence: NFIA ENST00000664495.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• 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: Ambry Genetics, Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000664495.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	ENST00000371191.5	TSL:5	c.96+25382G>T		intron	N/A	ENSP00000360233.1	B1AKN8
	NFIA	ENST00000664495.1		n.96+25382G>T		intron	N/A	ENSP00000499306.1	A0A590UJ67

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16699 AN: 152070 Hom.: 956 Cov.: 32

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.110 AC: 16717 AN: 152188 Hom.: 960 Cov.: 32 AF XY: 0.110 AC XY: 8203 AN XY: 74414

African (AFR) AF: 0.0702 AC: 2917 AN: 41534

American (AMR) AF: 0.128 AC: 1950 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3466

East Asian (EAS) AF: 0.244 AC: 1261 AN: 5174

South Asian (SAS) AF: 0.145 AC: 698 AN: 4822

European-Finnish (FIN) AF: 0.101 AC: 1065 AN: 10582

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8055 AN: 67996

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.108 Hom.: 617

Bravo AF: 0.111

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.75
PhyloP100		-1.7
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: rs12122228;

hg19: chr1-61356520;