chr1-61408005-T-G

Variant names:

• chr1-61408005-T-G
• rs9436640
• NM_001134673.4:c.1420+1278T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.595 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.1420+1278T>G		intron	N/A	NP_001128145.1	Q12857-1
	NFIA	NM_001145512.2		c.1555+1278T>G		intron	N/A	NP_001138984.1	Q12857-4
	NFIA	NM_001145511.2		c.1396+1278T>G		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.1420+1278T>G		intron	N/A	ENSP00000384523.3	Q12857-1
	NFIA	ENST00000371187.7	TSL:1	c.1420+1278T>G		intron	N/A	ENSP00000360229.3	Q12857-2
	NFIA	ENST00000493627.1	TSL:1	c.55+1278T>G		intron	N/A	ENSP00000474817.1	S4R3W6

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

African (AFR) AF: 0.348 AC: 14434 AN: 41468

American (AMR) AF: 0.390 AC: 5967 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3466

East Asian (EAS) AF: 0.485 AC: 2503 AN: 5160

South Asian (SAS) AF: 0.613 AC: 2957 AN: 4822

European-Finnish (FIN) AF: 0.608 AC: 6439 AN: 10582

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.470 AC: 31966 AN: 67950

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.459 Hom.: 29856

Bravo AF: 0.415

Asia WGS AF: 0.576 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		0.38
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: rs9436640; hg19: chr1-61873677; COSMIC: COSV63609569; COSMIC: COSV63609569;