18-79396326-C-T

Variant names:

• chr18-79396326-C-T
• rs780732210
• NM_001278669.2:c.102C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001278669.2(NFATC1):​c.102C>T​(p.Gly34Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000493 in 1,257,146 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: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: NFATC1 NM_001278669.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.526
• Publications: 0 publications found

Genes affected

NFATC1 (HGNC:7775): (nuclear factor of activated T cells 1) The product of this gene is a component of the nuclear factor of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation, and an inducible nuclear component. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as cyclosporin A. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes. [provided by RefSeq, Jul 2013]

NFATC1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 18-79396326-C-T is Benign according to our data. Variant chr18-79396326-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2648826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.526 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 62 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278669.2. 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
	NFATC1	NM_001278669.2	MANE Select	c.102C>T	p.Gly34Gly	synonymous	Exon 1 of 10	NP_001265598.1	O95644-1
	NFATC1	NM_006162.5		c.102C>T	p.Gly34Gly	synonymous	Exon 1 of 10	NP_006153.2
	NFATC1	NM_172390.3		c.102C>T	p.Gly34Gly	synonymous	Exon 1 of 8	NP_765978.1	O95644-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	ENST00000427363.7	TSL:1 MANE Select	c.102C>T	p.Gly34Gly	synonymous	Exon 1 of 10	ENSP00000389377.2	O95644-1
	NFATC1	ENST00000253506.9	TSL:1	c.102C>T	p.Gly34Gly	synonymous	Exon 1 of 10	ENSP00000253506.5	O95644-4
	NFATC1	ENST00000591814.5	TSL:1	c.102C>T	p.Gly34Gly	synonymous	Exon 1 of 8	ENSP00000466194.1	O95644-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000613 AC: 6 AN: 97946 AF XY: 0.0000727

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: 0.0000282

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000493 AC: 62 AN: 1257146 Hom.: 0 Cov.: 31 AF XY: 0.0000581 AC XY: 36 AN XY: 619622

African (AFR) AF: 0.00 AC: 0 AN: 25536

American (AMR) AF: 0.00 AC: 0 AN: 25430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20606

East Asian (EAS) AF: 0.00 AC: 0 AN: 25634

South Asian (SAS) AF: 0.000538 AC: 35 AN: 65008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4358

European-Non Finnish (NFE) AF: 0.0000200 AC: 20 AN: 997784

Other (OTH) AF: 0.000142 AC: 7 AN: 49438

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Uncertain	0.98
PhyloP100		-0.53
PromoterAI		-0.11	Neutral

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: rs780732210; hg19: chr18-77156326;