1-61406543-GCCCCCCCC-GCCCCCCC

Variant names:

• chr1-61406543-GC-G
• rs58081092
• NM_001134673.4:c.1255-5delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001134673.4(NFIA):​c.1255-5delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1080 hom., cov: 0)
  • Exomes 𝑓: 0.099 (960 hom.)
• Consequence: NFIA NM_001134673.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.886
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 1-61406543-GC-G is Benign according to our data. Variant chr1-61406543-GC-G is described in ClinVar as Benign. ClinVar VariationId is 1251146.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	NM_001134673.4	MANE Select	c.1255-5delC		splice_region intron	N/A	NP_001128145.1	Q12857-1
	NFIA	NM_001145512.2		c.1390-5delC		splice_region intron	N/A	NP_001138984.1	Q12857-4
	NFIA	NM_001145511.2		c.1231-5delC		splice_region intron	N/A	NP_001138983.1	Q12857-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIA	ENST00000403491.8	TSL:1 MANE Select	c.1255-18delC		intron	N/A	ENSP00000384523.3	Q12857-1
	NFIA	ENST00000371187.7	TSL:1	c.1255-18delC		intron	N/A	ENSP00000360229.3	Q12857-2
	NFIA	ENST00000371189.8	TSL:2	c.1390-18delC		intron	N/A	ENSP00000360231.3	Q12857-4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 8664 AN: 63556 Hom.: 1078 Cov.: 0

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.0370

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.162 AC: 8961 AN: 55298 AF XY: 0.162

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.0993 AC: 79270 AN: 798410 Hom.: 960 Cov.: 0 AF XY: 0.106 AC XY: 42245 AN XY: 398866

African (AFR) AF: 0.246 AC: 4473 AN: 18170

American (AMR) AF: 0.124 AC: 2509 AN: 20242

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 1918 AN: 13356

East Asian (EAS) AF: 0.125 AC: 2423 AN: 19326

South Asian (SAS) AF: 0.155 AC: 7126 AN: 45992

European-Finnish (FIN) AF: 0.103 AC: 3230 AN: 31380

Middle Eastern (MID) AF: 0.0904 AC: 280 AN: 3098

European-Non Finnish (NFE) AF: 0.0874 AC: 53713 AN: 614914

Other (OTH) AF: 0.113 AC: 3598 AN: 31932

GnomAD4 genome AF: 0.136 AC: 8677 AN: 63588 Hom.: 1080 Cov.: 0 AF XY: 0.139 AC XY: 4117 AN XY: 29718

African (AFR) AF: 0.312 AC: 5923 AN: 18964

American (AMR) AF: 0.124 AC: 594 AN: 4788

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 102 AN: 1786

East Asian (EAS) AF: 0.120 AC: 260 AN: 2170

South Asian (SAS) AF: 0.0390 AC: 53 AN: 1358

European-Finnish (FIN) AF: 0.0564 AC: 157 AN: 2784

Middle Eastern (MID) AF: 0.149 AC: 14 AN: 94

European-Non Finnish (NFE) AF: 0.0482 AC: 1463 AN: 30368

Other (OTH) AF: 0.115 AC: 94 AN: 816

Alfa AF: 0.0112 Hom.: 12

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89
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: rs58081092; hg19: chr1-61872215; COSMIC: COSV107442882; COSMIC: COSV107442882;