rs10489909

chr1-61397811-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.1076-6293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 152,264 control chromosomes in the GnomAD database, including 164 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 0.036 (164 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIA	NM_001134673.4	c.1076-6293C>T		intron_variant		ENST00000403491.8
NFIA	NM_001145511.2	c.1052-6293C>T		intron_variant
NFIA	NM_001145512.2	c.1211-6293C>T		intron_variant
NFIA	NM_005595.5	c.1076-6293C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIA	ENST00000403491.8	c.1076-6293C>T		intron_variant		1	NM_001134673.4	P1

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5488 AN: 152146 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.00888

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0360 AC: 5487 AN: 152264 Hom.: 164 Cov.: 32 AF XY: 0.0334 AC XY: 2487 AN XY: 74434

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.0419

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0182

Gnomad4 FIN AF: 0.00888

Gnomad4 NFE AF: 0.0560

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0506 Hom.: 121

Bravo AF: 0.0383

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.5
Dann	Benign	0.60

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: rs10489909; hg19: chr1-61863483;