rs41453448

Variant names:

• chr1-61358717-G-A
• rs41453448
• NM_001134673.4:c.819-430G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-61358717-G-A
• chr1-61358717-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.819-430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,064 control chromosomes in the GnomAD database, including 3,054 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 0.20 (3054 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.819-430G>A		intron_variant	Intron 5 of 10	ENST00000403491.8	NP_001128145.1
NFIA	NM_001145512.2	c.954-430G>A		intron_variant	Intron 6 of 11		NP_001138984.1
NFIA	NM_001145511.2	c.795-430G>A		intron_variant	Intron 5 of 10		NP_001138983.1
NFIA	NM_005595.5	c.819-430G>A		intron_variant	Intron 5 of 9		NP_005586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.819-430G>A		intron_variant	Intron 5 of 10	1	NM_001134673.4	ENSP00000384523.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29813 AN: 151946 Hom.: 3038 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.196 AC: 29867 AN: 152064 Hom.: 3054 Cov.: 32 AF XY: 0.200 AC XY: 14845 AN XY: 74292

African (AFR) AF: 0.203 AC: 8431 AN: 41476

American (AMR) AF: 0.192 AC: 2938 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1773 AN: 5154

South Asian (SAS) AF: 0.232 AC: 1116 AN: 4806

European-Finnish (FIN) AF: 0.187 AC: 1978 AN: 10586

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.183 AC: 12458 AN: 67984

Other (OTH) AF: 0.184 AC: 389 AN: 2110

Alfa AF: 0.193 Hom.: 1279

Bravo AF: 0.195

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.37
DANN	Benign	0.37
PhyloP100		-0.11
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: rs41453448; hg19: chr1-61824389; COSMIC: COSV64535224;