rs1909118

Variant names:

• chr1-61092333-G-A
• rs1909118
• NM_001134673.4:c.559+3653G>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+3653G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,158 control chromosomes in the GnomAD database, including 3,324 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 0.19 (3324 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.559+3653G>A		intron_variant	Intron 2 of 10	ENST00000403491.8	NP_001128145.1
NFIA	NM_001145512.2	c.694+3653G>A		intron_variant	Intron 3 of 11		NP_001138984.1
NFIA	NM_001145511.2	c.535+3653G>A		intron_variant	Intron 2 of 10		NP_001138983.1
NFIA	NM_005595.5	c.559+3653G>A		intron_variant	Intron 2 of 9		NP_005586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.559+3653G>A		intron_variant	Intron 2 of 10	1	NM_001134673.4	ENSP00000384523.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29531 AN: 152038 Hom.: 3302 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.195 AC: 29598 AN: 152158 Hom.: 3324 Cov.: 32 AF XY: 0.195 AC XY: 14517 AN XY: 74392

African (AFR) AF: 0.251 AC: 10402 AN: 41514

American (AMR) AF: 0.190 AC: 2909 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2617 AN: 5172

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4824

European-Finnish (FIN) AF: 0.122 AC: 1295 AN: 10592

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10303 AN: 67970

Other (OTH) AF: 0.172 AC: 363 AN: 2112

Alfa AF: 0.166 Hom.: 308

Bravo AF: 0.200

Asia WGS AF: 0.428 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.63
PhyloP100		-0.37
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: rs1909118; hg19: chr1-61558005;