1-61272598-C-T

Variant names:

• chr1-61272598-C-T
• rs437021
• NM_001134673.4:c.560-4922C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134673.4(NFIA):​c.560-4922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,050 control chromosomes in the GnomAD database, including 12,170 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 0.37 (12170 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134673.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	NM_001134673.4	MANE Select	c.560-4922C>T		intron	N/A	NP_001128145.1	Q12857-1
	NFIA	NM_001145512.2		c.695-4922C>T		intron	N/A	NP_001138984.1	Q12857-4
	NFIA	NM_001145511.2		c.536-4922C>T		intron	N/A	NP_001138983.1	Q12857-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	ENST00000403491.8	TSL:1 MANE Select	c.560-4922C>T		intron	N/A	ENSP00000384523.3	Q12857-1
	NFIA	ENST00000371187.7	TSL:1	c.560-4922C>T		intron	N/A	ENSP00000360229.3	Q12857-2
	NFIA	ENST00000371189.8	TSL:2	c.695-4922C>T		intron	N/A	ENSP00000360231.3	Q12857-4

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55622 AN: 151932 Hom.: 12163 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.366 AC: 55638 AN: 152050 Hom.: 12170 Cov.: 32 AF XY: 0.370 AC XY: 27492 AN XY: 74334

African (AFR) AF: 0.114 AC: 4751 AN: 41516

American (AMR) AF: 0.492 AC: 7518 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3466

East Asian (EAS) AF: 0.466 AC: 2401 AN: 5156

South Asian (SAS) AF: 0.396 AC: 1913 AN: 4828

European-Finnish (FIN) AF: 0.469 AC: 4945 AN: 10540

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31274 AN: 67952

Other (OTH) AF: 0.386 AC: 815 AN: 2110

Alfa AF: 0.440 Hom.: 47856

Bravo AF: 0.363

Asia WGS AF: 0.375 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.48
DANN	Benign	0.21
PhyloP100		-1.0
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: rs437021; hg19: chr1-61738270;