rs9436636

Variant names:

• chr1-61347101-G-A
• rs9436636
• NM_001134673.4:c.701-5349G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-61347101-G-A
• chr1-61347101-G-T

Variant summary

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

The NM_001134673.4(NFIA):​c.701-5349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 149,918 control chromosomes in the GnomAD database, including 13,074 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 0.41 (13074 hom., cov: 28)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.701-5349G>A		intron_variant	Intron 4 of 10	ENST00000403491.8	NP_001128145.1
NFIA	NM_001145512.2	c.836-5349G>A		intron_variant	Intron 5 of 11		NP_001138984.1
NFIA	NM_001145511.2	c.677-5349G>A		intron_variant	Intron 4 of 10		NP_001138983.1
NFIA	NM_005595.5	c.701-5349G>A		intron_variant	Intron 4 of 9		NP_005586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.701-5349G>A		intron_variant	Intron 4 of 10	1	NM_001134673.4	ENSP00000384523.3

Frequencies

GnomAD3 genomes AF: 0.411 AC: 61544 AN: 149796 Hom.: 13061 Cov.: 28

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.411 AC: 61604 AN: 149918 Hom.: 13074 Cov.: 28 AF XY: 0.409 AC XY: 29841 AN XY: 73022

African (AFR) AF: 0.497 AC: 20278 AN: 40808

American (AMR) AF: 0.353 AC: 5323 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1585 AN: 3460

East Asian (EAS) AF: 0.280 AC: 1399 AN: 5004

South Asian (SAS) AF: 0.234 AC: 1095 AN: 4684

European-Finnish (FIN) AF: 0.435 AC: 4345 AN: 9992

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.386 AC: 26109 AN: 67628

Other (OTH) AF: 0.422 AC: 875 AN: 2072

Alfa AF: 0.390 Hom.: 35511

Bravo AF: 0.408

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.89
DANN	Benign	0.33
PhyloP100		-0.54
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: rs9436636; hg19: chr1-61812773;