rs9436640

Positions:

• chr1-61408005-T-G

Variant summary

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

The NM_001134673.4(NFIA):​c.1420+1278T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,046 control chromosomes in the GnomAD database, including 15,330 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 0.44 (15330 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFIA	NM_001134673.4	c.1420+1278T>G		intron_variant		ENST00000403491.8
NFIA	NM_001145511.2	c.1396+1278T>G		intron_variant
NFIA	NM_001145512.2	c.1555+1278T>G		intron_variant
NFIA	NM_005595.5	c.1420+1278T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIA	ENST00000403491.8	c.1420+1278T>G		intron_variant		1	NM_001134673.4	P1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67084 AN: 151928 Hom.: 15307 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.442 AC: 67148 AN: 152046 Hom.: 15330 Cov.: 32 AF XY: 0.449 AC XY: 33388 AN XY: 74324

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.456

Alfa AF: 0.452 Hom.: 9993

Bravo AF: 0.415

Asia WGS AF: 0.576 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.75

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: rs9436640; hg19: chr1-61873677; COSMIC: COSV63609569; COSMIC: COSV63609569;