NM_001134673.4:c.559+66144A>G

Variant names:

• chr1-61154824-A-G
• rs334699
• NM_001134673.4:c.559+66144A>G

Variant summary

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

The NM_001134673.4(NFIA):​c.559+66144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,296 control chromosomes in the GnomAD database, including 65,521 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 0.93 (65521 hom., cov: 33)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 21 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.559+66144A>G		intron_variant	Intron 2 of 10	ENST00000403491.8	NP_001128145.1
NFIA	NM_001145512.2	c.694+66144A>G		intron_variant	Intron 3 of 11		NP_001138984.1
NFIA	NM_001145511.2	c.535+66144A>G		intron_variant	Intron 2 of 10		NP_001138983.1
NFIA	NM_005595.5	c.559+66144A>G		intron_variant	Intron 2 of 9		NP_005586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.559+66144A>G		intron_variant	Intron 2 of 10	1	NM_001134673.4	ENSP00000384523.3

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140964 AN: 152178 Hom.: 65466 Cov.: 33

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.926 AC: 141078 AN: 152296 Hom.: 65521 Cov.: 33 AF XY: 0.929 AC XY: 69197 AN XY: 74472

African (AFR) AF: 0.850 AC: 35313 AN: 41530

American (AMR) AF: 0.951 AC: 14564 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3268 AN: 3472

East Asian (EAS) AF: 0.947 AC: 4904 AN: 5176

South Asian (SAS) AF: 0.918 AC: 4431 AN: 4826

European-Finnish (FIN) AF: 0.982 AC: 10428 AN: 10624

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 65010 AN: 68042

Other (OTH) AF: 0.941 AC: 1987 AN: 2112

Alfa AF: 0.941 Hom.: 114000

Bravo AF: 0.922

Asia WGS AF: 0.898 AC: 3122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.54
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs334699; hg19: chr1-61620496;