rs777624713

Variant names:

• chr1-61406553-C-CA
• rs777624713
• NM_001134673.4:c.1255-9_1255-8insA

Your query was ambiguous. Multiple possible variants found:

• chr1-61406553-C-CA
• chr1-61406553-C-CG
• chr1-61406553-C-CT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001134673.4(NFIA):​c.1255-9_1255-8insA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,198,484 control chromosomes in the GnomAD database, including 1 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 0.00026 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00013 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: NFIA NM_001134673.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.165
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 1-61406553-C-CA is Benign according to our data. Variant chr1-61406553-C-CA is described in ClinVar as Likely_benign. ClinVar VariationId is 435979.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 158 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.1255-9_1255-8insA		splice_region intron	N/A	NP_001128145.1
	NFIA	NM_001145512.2		c.1390-9_1390-8insA		splice_region intron	N/A	NP_001138984.1
	NFIA	NM_001145511.2		c.1231-9_1231-8insA		splice_region 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.1255-9_1255-8insA		splice_region intron	N/A	ENSP00000384523.3
	NFIA	ENST00000371187.7	TSL:1	c.1255-9_1255-8insA		splice_region intron	N/A	ENSP00000360229.3
	NFIA	ENST00000371189.8	TSL:2	c.1390-9_1390-8insA		splice_region intron	N/A	ENSP00000360231.3

Frequencies

GnomAD3 genomes AF: 0.000257 AC: 31 AN: 120848 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000594

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000524

Gnomad OTH AF: 0.000654

GnomAD2 exomes AF: 0.0000853 AC: 12 AN: 140716 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

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: 0.000151

Gnomad OTH exome AF: 0.000638

GnomAD4 exome AF: 0.000132 AC: 158 AN: 1198484 Hom.: 1 Cov.: 24 AF XY: 0.000136 AC XY: 81 AN XY: 595798

African (AFR) AF: 0.00 AC: 0 AN: 27040

American (AMR) AF: 0.00 AC: 0 AN: 32324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20276

East Asian (EAS) AF: 0.0000370 AC: 1 AN: 27052

South Asian (SAS) AF: 0.0000146 AC: 1 AN: 68294

European-Finnish (FIN) AF: 0.0000233 AC: 1 AN: 42838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4746

European-Non Finnish (NFE) AF: 0.000156 AC: 145 AN: 927774

Other (OTH) AF: 0.000208 AC: 10 AN: 48140

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000256 AC: 31 AN: 120938 Hom.: 0 Cov.: 24 AF XY: 0.000186 AC XY: 11 AN XY: 59104

African (AFR) AF: 0.0000592 AC: 2 AN: 33758

American (AMR) AF: 0.00 AC: 0 AN: 12296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3018

East Asian (EAS) AF: 0.00 AC: 0 AN: 3810

South Asian (SAS) AF: 0.00 AC: 0 AN: 2974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.000524 AC: 28 AN: 53404

Other (OTH) AF: 0.000648 AC: 1 AN: 1544

Alfa AF: 0.0000966 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	NFIA-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs777624713; hg19: chr1-61872225;