rs7521242

Variant names:

• chr1-61338217-G-A
• rs7521242
• NM_001134673.4:c.700+5631G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-61338217-G-A
• chr1-61338217-G-C

Variant summary

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

The NM_001134673.4(NFIA):​c.700+5631G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,986 control chromosomes in the GnomAD database, including 17,258 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 0.47 (17258 hom., cov: 33)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573
• Publications: 8 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=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 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.700+5631G>A		intron	N/A	NP_001128145.1	Q12857-1
	NFIA	NM_001145512.2		c.835+5631G>A		intron	N/A	NP_001138984.1	Q12857-4
	NFIA	NM_001145511.2		c.676+5631G>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.700+5631G>A		intron	N/A	ENSP00000384523.3	Q12857-1
	NFIA	ENST00000371187.7	TSL:1	c.700+5631G>A		intron	N/A	ENSP00000360229.3	Q12857-2
	NFIA	ENST00000371189.8	TSL:2	c.835+5631G>A		intron	N/A	ENSP00000360231.3	Q12857-4

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71306 AN: 151868 Hom.: 17241 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.470 AC: 71373 AN: 151986 Hom.: 17258 Cov.: 33 AF XY: 0.474 AC XY: 35227 AN XY: 74282

African (AFR) AF: 0.402 AC: 16655 AN: 41426

American (AMR) AF: 0.548 AC: 8379 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1475 AN: 3468

East Asian (EAS) AF: 0.650 AC: 3346 AN: 5150

South Asian (SAS) AF: 0.597 AC: 2874 AN: 4814

European-Finnish (FIN) AF: 0.469 AC: 4954 AN: 10558

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32183 AN: 67966

Other (OTH) AF: 0.464 AC: 976 AN: 2104

Alfa AF: 0.468 Hom.: 27531

Bravo AF: 0.474

Asia WGS AF: 0.625 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		0.57
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: rs7521242; hg19: chr1-61803889;