18-79396207-C-CCCG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001278669.2(NFATC1):c.-7_-5dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000805 in 1,470,272 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00042 (2 hom.)
• Consequence: NFATC1 NM_001278669.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.279

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 18-79396207-C-CCCG is Benign according to our data. Variant chr18-79396207-C-CCCG is described in ClinVar as [Benign]. Clinvar id is 3044671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 635 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC1	NM_001278669.2	c.-7_-5dup		5_prime_UTR_variant	1/10	ENST00000427363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC1	ENST00000427363.7	c.-7_-5dup		5_prime_UTR_variant	1/10	1	NM_001278669.2	P4

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 635 AN: 151422 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000777

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.000435 AC: 63 AN: 144692 Hom.: 0 AF XY: 0.000341 AC XY: 28 AN XY: 82130

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.000179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000266

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000323

Gnomad OTH exome AF: 0.000304

GnomAD4 exome AF: 0.000417 AC: 550 AN: 1318742 Hom.: 2 Cov.: 31 AF XY: 0.000372 AC XY: 243 AN XY: 654100

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.000277

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00331

Gnomad4 SAS exome AF: 0.0000406

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000193

Gnomad4 OTH exome AF: 0.000844

GnomAD4 genome AF: 0.00418 AC: 634 AN: 151530 Hom.: 2 Cov.: 31 AF XY: 0.00390 AC XY: 289 AN XY: 74070

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.00125

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000779

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.000475

Asia WGS AF: 0.00123 AC: 4 AN: 3276

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NFATC1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 07, 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs565670974; hg19: chr18-77156207;