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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001134673.4(NFIA):c.1255-7_1255-5delCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00751 in 872,130 control chromosomes in the GnomAD database, including 102 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 29 hom., cov: 0)

Exomes 𝑓: 0.0074 ( 73 hom. )

Consequence

NFIA
NM_001134673.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter 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:

NFIA (HGNC:):

NFIA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-61406543-GCCC-G is Benign according to our data. Variant chr1-61406543-GCCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1219266.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00863 (551/63870) while in subpopulation AFR AF= 0.0262 (502/19124). AF 95% confidence interval is 0.0244. There are 29 homozygotes in gnomad4. There are 243 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 551 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NFIA	NM_001134673.4 linkuse as main transcript	c.1255-7_1255-5delCCC	splice_region_variant, intron_variant	ENST00000403491.8	NP_001128145.1	Q12857-1
NFIA	NM_001145512.2 linkuse as main transcript	c.1390-7_1390-5delCCC	splice_region_variant, intron_variant		NP_001138984.1	Q12857-4
NFIA	NM_001145511.2 linkuse as main transcript	c.1231-7_1231-5delCCC	splice_region_variant, intron_variant		NP_001138983.1	Q12857-3
NFIA	NM_005595.5 linkuse as main transcript	c.1255-7_1255-5delCCC	splice_region_variant, intron_variant		NP_005586.1	Q12857-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8 linkuse as main transcript	c.1255-7_1255-5delCCC		splice_region_variant, intron_variant		1	NM_001134673.4	ENSP00000384523.3		Q12857-1

Frequencies

GnomAD3 genomes

AF:

0.00860

AC:

549

AN:

63834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00292

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.000715

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000788

Gnomad OTH

AF:

0.00489

GnomAD3 exomes

AF:

0.0229

AC:

1264

AN:

55298

Hom.:

AF XY:

0.0217

AC XY:

661

AN XY:

30448

show subpopulations

Gnomad AFR exome

AF:

0.0630

Gnomad AMR exome

AF:

0.0358

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.0193

Gnomad SAS exome

AF:

0.0186

Gnomad FIN exome

AF:

0.00862

Gnomad NFE exome

AF:

0.0166

Gnomad OTH exome

AF:

0.0172

GnomAD4 exome

AF:

0.00743

AC:

6002

AN:

808260

Hom.:

AF XY:

0.00772

AC XY:

3120

AN XY:

404264

show subpopulations

Gnomad4 AFR exome

AF:

0.0404

Gnomad4 AMR exome

AF:

0.0178

Gnomad4 ASJ exome

AF:

0.00691

Gnomad4 EAS exome

AF:

0.00526

Gnomad4 SAS exome

AF:

0.00928

Gnomad4 FIN exome

AF:

0.00488

Gnomad4 NFE exome

AF:

0.00609

Gnomad4 OTH exome

AF:

0.00901

GnomAD4 genome

AF:

0.00863

AC:

551

AN:

63870

Hom.:

Cov.:

AF XY:

0.00814

AC XY:

243

AN XY:

29850

show subpopulations

Gnomad4 AFR

AF:

0.0262

Gnomad4 AMR

AF:

0.00292

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00368

Gnomad4 FIN

AF:

0.000715

Gnomad4 NFE

AF:

0.000788

Gnomad4 OTH

AF:

0.00485

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2019

- -

NFIA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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