chr1-61406720-G-T

Variant names:

• chr1-61406720-G-T
• rs146012018
• NM_001134673.4:c.1413G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001134673.4(NFIA):​c.1413G>T​(p.Thr471Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,607,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T471T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NFIA NM_001134673.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.924
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-61406720-G-T is Benign according to our data. Variant chr1-61406720-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2916162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.924 with no splicing effect.
• BS2: High AC in GnomAd4 at 6 AD gene.

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.1413G>T	p.Thr471Thr	synonymous	Exon 9 of 11	NP_001128145.1
	NFIA	NM_001145512.2		c.1548G>T	p.Thr516Thr	synonymous	Exon 10 of 12	NP_001138984.1
	NFIA	NM_001145511.2		c.1389G>T	p.Thr463Thr	synonymous	Exon 9 of 11	NP_001138983.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	ENST00000403491.8	TSL:1 MANE Select	c.1413G>T	p.Thr471Thr	synonymous	Exon 9 of 11	ENSP00000384523.3
	NFIA	ENST00000371187.7	TSL:1	c.1413G>T	p.Thr471Thr	synonymous	Exon 9 of 10	ENSP00000360229.3
	NFIA	ENST00000493627.1	TSL:1	c.48G>T	p.Thr16Thr	synonymous	Exon 1 of 3	ENSP00000474817.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152104 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000126 AC: 3 AN: 238554 AF XY: 0.00

Gnomad AFR exome AF: 0.000197

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455548 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 723472

African (AFR) AF: 0.0000899 AC: 3 AN: 33356

American (AMR) AF: 0.0000227 AC: 1 AN: 43968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39442

South Asian (SAS) AF: 0.00 AC: 0 AN: 84668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109086

Other (OTH) AF: 0.00 AC: 0 AN: 60192

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152222 Hom.: 0 Cov.: 30 AF XY: 0.0000537 AC XY: 4 AN XY: 74422

African (AFR) AF: 0.000120 AC: 5 AN: 41536

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 13, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		0.92
PromoterAI		-0.12	Neutral
Mutation Taster		=93/7	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: rs146012018; hg19: chr1-61872392;