1-61350127-A-T

Variant names:

• chr1-61350127-A-T
• rs41350144
• NM_001134673.4:c.701-2323A>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.701-2323A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,022 control chromosomes in the GnomAD database, including 15,171 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 0.43 (15171 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.701-2323A>T		intron_variant	Intron 4 of 10	ENST00000403491.8	NP_001128145.1
NFIA	NM_001145512.2	c.836-2323A>T		intron_variant	Intron 5 of 11		NP_001138984.1
NFIA	NM_001145511.2	c.677-2323A>T		intron_variant	Intron 4 of 10		NP_001138983.1
NFIA	NM_005595.5	c.701-2323A>T		intron_variant	Intron 4 of 9		NP_005586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.701-2323A>T		intron_variant	Intron 4 of 10	1	NM_001134673.4	ENSP00000384523.3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64953 AN: 151904 Hom.: 15167 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.427 AC: 64982 AN: 152022 Hom.: 15171 Cov.: 32 AF XY: 0.434 AC XY: 32265 AN XY: 74320

African (AFR) AF: 0.250 AC: 10371 AN: 41478

American (AMR) AF: 0.538 AC: 8215 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1468 AN: 3466

East Asian (EAS) AF: 0.664 AC: 3426 AN: 5158

South Asian (SAS) AF: 0.603 AC: 2905 AN: 4816

European-Finnish (FIN) AF: 0.470 AC: 4960 AN: 10556

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32176 AN: 67950

Other (OTH) AF: 0.441 AC: 932 AN: 2112

Alfa AF: 0.295 Hom.: 772

Bravo AF: 0.426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.44
DANN	Benign	0.46
PhyloP100		-0.24
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: rs41350144; hg19: chr1-61815799;