chr1-61397811-C-T

Variant names:

• chr1-61397811-C-T
• rs10489909
• NM_001134673.4:c.1076-6293C>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.1076-6293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 152,264 control chromosomes in the GnomAD database, including 164 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 0.036 (164 hom., cov: 32)
• Consequence: NFIA NM_001134673.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.0545 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.1076-6293C>T		intron	N/A	NP_001128145.1
	NFIA	NM_001145512.2		c.1211-6293C>T		intron	N/A	NP_001138984.1
	NFIA	NM_001145511.2		c.1052-6293C>T		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.1076-6293C>T		intron	N/A	ENSP00000384523.3
	NFIA	ENST00000371187.7	TSL:1	c.1076-6293C>T		intron	N/A	ENSP00000360229.3
	NFIA	ENST00000371189.8	TSL:2	c.1211-6293C>T		intron	N/A	ENSP00000360231.3

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5488 AN: 152146 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.00888

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0360 AC: 5487 AN: 152264 Hom.: 164 Cov.: 32 AF XY: 0.0334 AC XY: 2487 AN XY: 74434

African (AFR) AF: 0.0115 AC: 478 AN: 41560

American (AMR) AF: 0.0419 AC: 640 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0182 AC: 88 AN: 4824

European-Finnish (FIN) AF: 0.00888 AC: 94 AN: 10590

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0560 AC: 3810 AN: 68028

Other (OTH) AF: 0.0492 AC: 104 AN: 2114

Alfa AF: 0.0492 Hom.: 158

Bravo AF: 0.0383

Asia WGS AF: 0.00722 AC: 26 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	4.5
DANN	Benign	0.60
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

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: rs10489909; hg19: chr1-61863483;