rs766488

Variant names:

• chr1-61344843-G-A
• rs766488
• NM_001134673.4:c.701-7607G>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.701-7607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,006 control chromosomes in the GnomAD database, including 10,700 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 0.36 (10700 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.858
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	NM_001134673.4	MANE Select	c.701-7607G>A		intron	N/A	NP_001128145.1	Q12857-1
	NFIA	NM_001145512.2		c.836-7607G>A		intron	N/A	NP_001138984.1	Q12857-4
	NFIA	NM_001145511.2		c.677-7607G>A		intron	N/A	NP_001138983.1	Q12857-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	ENST00000403491.8	TSL:1 MANE Select	c.701-7607G>A		intron	N/A	ENSP00000384523.3	Q12857-1
	NFIA	ENST00000371187.7	TSL:1	c.701-7607G>A		intron	N/A	ENSP00000360229.3	Q12857-2
	NFIA	ENST00000371189.8	TSL:2	c.836-7607G>A		intron	N/A	ENSP00000360231.3	Q12857-4

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54634 AN: 151888 Hom.: 10685 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.360 AC: 54700 AN: 152006 Hom.: 10700 Cov.: 32 AF XY: 0.359 AC XY: 26653 AN XY: 74292

African (AFR) AF: 0.493 AC: 20424 AN: 41450

American (AMR) AF: 0.305 AC: 4660 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.0856 AC: 444 AN: 5186

South Asian (SAS) AF: 0.207 AC: 993 AN: 4800

European-Finnish (FIN) AF: 0.374 AC: 3939 AN: 10546

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21755 AN: 67952

Other (OTH) AF: 0.354 AC: 746 AN: 2110

Alfa AF: 0.329 Hom.: 26702

Bravo AF: 0.361

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.4
DANN	Benign	0.60
PhyloP100		0.86
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: rs766488; hg19: chr1-61810515;