Variant 1-61406543-GCCCC-GCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001134673.4(NFIA):c.1255-6_1255-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 863,634 control chromosomes in the GnomAD database, including 846 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 326 hom., cov: 0)

Exomes 𝑓: 0.035 ( 520 hom. )

Consequence

NFIA
NM_001134673.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.886

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-61406543-GCC-G is Benign according to our data. Variant chr1-61406543-GCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 445456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NFIA	NM_001134673.4 linkuse as main transcript	c.1255-6_1255-5del	splice_polypyrimidine_tract_variant, intron_variant	ENST00000403491.8
NFIA	NM_001145511.2 linkuse as main transcript	c.1231-6_1231-5del	splice_polypyrimidine_tract_variant, intron_variant
NFIA	NM_001145512.2 linkuse as main transcript	c.1390-6_1390-5del	splice_polypyrimidine_tract_variant, intron_variant
NFIA	NM_005595.5 linkuse as main transcript	c.1255-6_1255-5del	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFIA	ENST00000403491.8 linkuse as main transcript	c.1255-6_1255-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001134673.4	P1	Q12857-1

Frequencies

GnomAD3 genomes

AF:

0.0545

AC:

3477

AN:

63764

Hom.:

324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0313

Gnomad ASJ

AF:

0.00783

Gnomad EAS

AF:

0.00321

Gnomad SAS

AF:

0.000727

Gnomad FIN

AF:

0.00430

Gnomad MID

AF:

0.0306

Gnomad NFE

AF:

0.00535

Gnomad OTH

AF:

0.0440

GnomAD3 exomes

AF:

0.0748

AC:

4137

AN:

55298

Hom.:

AF XY:

0.0686

AC XY:

2089

AN XY:

30448

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.0631

Gnomad EAS exome

AF:

0.0577

Gnomad SAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.0463

Gnomad NFE exome

AF:

0.0523

Gnomad OTH exome

AF:

0.0840

GnomAD4 exome

AF:

0.0351

AC:

28090

AN:

799836

Hom.:

520

AF XY:

0.0367

AC XY:

14679

AN XY:

399808

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.0716

Gnomad4 ASJ exome

AF:

0.0414

Gnomad4 EAS exome

AF:

0.0319

Gnomad4 SAS exome

AF:

0.0470

Gnomad4 FIN exome

AF:

0.0346

Gnomad4 NFE exome

AF:

0.0285

Gnomad4 OTH exome

AF:

0.0429

GnomAD4 genome

AF:

0.0549

AC:

3501

AN:

63798

Hom.:

326

Cov.:

AF XY:

0.0546

AC XY:

1629

AN XY:

29818

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.0311

Gnomad4 ASJ

AF:

0.00783

Gnomad4 EAS

AF:

0.00322

Gnomad4 SAS

AF:

0.000736

Gnomad4 FIN

AF:

0.00430

Gnomad4 NFE

AF:

0.00535

Gnomad4 OTH

AF:

0.0437

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 03, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 12, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over