NM_001134673.4:c.626-6321G>A

Variant names:

• chr1-61326191-G-A
• rs6691768
• NM_001134673.4:c.626-6321G>A

Variant summary

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

The NM_001134673.4(NFIA):​c.626-6321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,836 control chromosomes in the GnomAD database, including 22,509 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 0.51 (22509 hom., cov: 30)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 20 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.688 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	NM_001134673.4	MANE Select	c.626-6321G>A		intron	N/A	NP_001128145.1
	NFIA	NM_001145512.2		c.761-6321G>A		intron	N/A	NP_001138984.1
	NFIA	NM_001145511.2		c.602-6321G>A		intron	N/A	NP_001138983.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	ENST00000403491.8	TSL:1 MANE Select	c.626-6321G>A		intron	N/A	ENSP00000384523.3
	NFIA	ENST00000371187.7	TSL:1	c.626-6321G>A		intron	N/A	ENSP00000360229.3
	NFIA	ENST00000371189.8	TSL:2	c.761-6321G>A		intron	N/A	ENSP00000360231.3

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77858 AN: 151718 Hom.: 22503 Cov.: 30

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.513 AC: 77893 AN: 151836 Hom.: 22509 Cov.: 30 AF XY: 0.520 AC XY: 38575 AN XY: 74180

African (AFR) AF: 0.231 AC: 9582 AN: 41438

American (AMR) AF: 0.673 AC: 10269 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1752 AN: 3464

East Asian (EAS) AF: 0.671 AC: 3438 AN: 5124

South Asian (SAS) AF: 0.708 AC: 3411 AN: 4818

European-Finnish (FIN) AF: 0.595 AC: 6257 AN: 10514

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41303 AN: 67912

Other (OTH) AF: 0.538 AC: 1135 AN: 2108

Alfa AF: 0.583 Hom.: 100115

Bravo AF: 0.508

Asia WGS AF: 0.689 AC: 2399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.20
PhyloP100		-0.65
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: rs6691768; hg19: chr1-61791863;