chr18-79400385-A-ACCCGC

Position:

• chr18-79400385-A-ACCCGC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The ENST00000329101.8(NFATC1):​c.-5_-1dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,044,608 control chromosomes in the GnomAD database, including 30 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.010 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (13 hom.)
• Consequence: NFATC1 ENST00000329101.8 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.11

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 Benign. Variant got -9 ACMG points.

• BP6: Variant 18-79400385-A-ACCCGC is Benign according to our data. Variant chr18-79400385-A-ACCCGC is described in ClinVar as [Benign]. Clinvar id is 3053678.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1215/120136) while in subpopulation AFR AF= 0.0328 (1074/32792). AF 95% confidence interval is 0.0311. There are 17 homozygotes in gnomad4. There are 580 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1215 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFATC1	NM_001278669.2	c.127+4036_127+4040dup		intron_variant		ENST00000427363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFATC1	ENST00000427363.7	c.127+4036_127+4040dup		intron_variant		1	NM_001278669.2	P4

Frequencies

GnomAD3 genomes AF: 0.00994 AC: 1193 AN: 120028 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000281

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00490

Gnomad NFE AF: 0.000466

Gnomad OTH AF: 0.00730

GnomAD3 exomes AF: 0.00190 AC: 124 AN: 65168 Hom.: 2 AF XY: 0.00199 AC XY: 72 AN XY: 36134

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.00132

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000863

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000466

Gnomad OTH exome AF: 0.00374

GnomAD4 exome AF: 0.00162 AC: 1500 AN: 924472 Hom.: 13 Cov.: 31 AF XY: 0.00152 AC XY: 710 AN XY: 466544

Gnomad4 AFR exome AF: 0.0393

Gnomad4 AMR exome AF: 0.00290

Gnomad4 ASJ exome AF: 0.0102

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000113

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000268

Gnomad4 OTH exome AF: 0.00584

GnomAD4 genome AF: 0.0101 AC: 1215 AN: 120136 Hom.: 17 Cov.: 32 AF XY: 0.00988 AC XY: 580 AN XY: 58678

Gnomad4 AFR AF: 0.0328

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000280

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000466

Gnomad4 OTH AF: 0.00722

Alfa AF: 0.00725 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NFATC1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 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: rs749645871; hg19: chr18-77160385;