rs12568010

Positions:

• chr1-61366266-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134673.4(NFIA):​c.946+6992A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 152,166 control chromosomes in the GnomAD database, including 912 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 0.098 (912 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIA	NM_001134673.4	c.946+6992A>G		intron_variant		ENST00000403491.8
NFIA	NM_001145511.2	c.922+6992A>G		intron_variant
NFIA	NM_001145512.2	c.1081+6992A>G		intron_variant
NFIA	NM_005595.5	c.946+6992A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIA	ENST00000403491.8	c.946+6992A>G		intron_variant		1	NM_001134673.4	P1

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14905 AN: 152048 Hom.: 911 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.0981 AC: 14929 AN: 152166 Hom.: 912 Cov.: 32 AF XY: 0.0950 AC XY: 7066 AN XY: 74392

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0390

Gnomad4 FIN AF: 0.0545

Gnomad4 NFE AF: 0.0709

Gnomad4 OTH AF: 0.0946

Alfa AF: 0.0782 Hom.: 903

Bravo AF: 0.104

Asia WGS AF: 0.119 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.060
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs12568010; hg19: chr1-61831938;