rs1125777

Positions:

• chr1-61366218-C-T

Variant summary

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

The NM_001134673.4(NFIA):​c.946+6944C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,944 control chromosomes in the GnomAD database, including 15,109 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 0.43 (15109 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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 = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.946+6944C>T		intron_variant		ENST00000403491.8	NP_001128145.1
NFIA	NM_001145511.2	c.922+6944C>T		intron_variant			NP_001138983.1
NFIA	NM_001145512.2	c.1081+6944C>T		intron_variant			NP_001138984.1
NFIA	NM_005595.5	c.946+6944C>T		intron_variant			NP_005586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.946+6944C>T		intron_variant		1	NM_001134673.4	ENSP00000384523	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65130 AN: 151824 Hom.: 15103 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.429 AC: 65171 AN: 151944 Hom.: 15109 Cov.: 32 AF XY: 0.436 AC XY: 32356 AN XY: 74222

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.437

Alfa AF: 0.472 Hom.: 34754

Bravo AF: 0.427

Asia WGS AF: 0.627 AC: 2185 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	2.9
DANN	Benign	0.62

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: rs1125777; hg19: chr1-61831890;