chr1-61082809-T-C

Position:

• chr1-61082809-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001134673.4(NFIA):​c.18T>C​(p.Cys6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000716 in 1,396,640 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 (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: NFIA NM_001134673.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.39

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-61082809-T-C is Benign according to our data. Variant chr1-61082809-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2083104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIA	NM_001134673.4	c.18T>C	p.Cys6=	synonymous_variant	1/11	ENST00000403491.8	NP_001128145.1
NFIA	NM_001145512.2	c.153T>C	p.Cys51=	synonymous_variant	2/12		NP_001138984.1
NFIA	NM_005595.5	c.18T>C	p.Cys6=	synonymous_variant	1/10		NP_005586.1
NFIA	NM_001145511.2	c.3+5181T>C		intron_variant			NP_001138983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIA	ENST00000403491.8	c.18T>C	p.Cys6=	synonymous_variant	1/11	1	NM_001134673.4	ENSP00000384523	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD3 exomes AF: 0.0000584 AC: 9 AN: 154158 Hom.: 0 AF XY: 0.0000246 AC XY: 2 AN XY: 81288

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000364

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000716 AC: 10 AN: 1396640 Hom.: 0 Cov.: 39 AF XY: 0.00000435 AC XY: 3 AN XY: 689062

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000281

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs777375238; hg19: chr1-61548481;