1-61144377-G-A

Variant names:

• chr1-61144377-G-A
• rs334725
• NM_001134673.4:c.559+55697G>A

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+55697G>A 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 152,270 control chromosomes in the GnomAD database, including 65,512 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 (65512 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134673.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	NM_001134673.4	MANE Select	c.559+55697G>A		intron	N/A	NP_001128145.1
	NFIA	NM_001145512.2		c.694+55697G>A		intron	N/A	NP_001138984.1
	NFIA	NM_001145511.2		c.535+55697G>A		intron	N/A	NP_001138983.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	ENST00000403491.8	TSL:1 MANE Select	c.559+55697G>A		intron	N/A	ENSP00000384523.3
	NFIA	ENST00000371187.7	TSL:1	c.559+55697G>A		intron	N/A	ENSP00000360229.3
	NFIA	ENST00000371189.8	TSL:2	c.694+55697G>A		intron	N/A	ENSP00000360231.3

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140941 AN: 152152 Hom.: 65457 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.981

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.926 AC: 141055 AN: 152270 Hom.: 65512 Cov.: 32 AF XY: 0.929 AC XY: 69165 AN XY: 74438

African (AFR) AF: 0.851 AC: 35318 AN: 41516

American (AMR) AF: 0.951 AC: 14554 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3266 AN: 3470

East Asian (EAS) AF: 0.947 AC: 4903 AN: 5180

South Asian (SAS) AF: 0.918 AC: 4433 AN: 4828

European-Finnish (FIN) AF: 0.981 AC: 10424 AN: 10622

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 65000 AN: 68038

Other (OTH) AF: 0.940 AC: 1986 AN: 2112

Alfa AF: 0.948 Hom.: 38813

Bravo AF: 0.922

Asia WGS AF: 0.898 AC: 3122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.61
PhyloP100		0.30
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: rs334725; hg19: chr1-61610049;