rs9518

Positions:

• chr18-79528806-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000427363.7(NFATC1):​c.*1229T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,436 control chromosomes in the GnomAD database, including 14,321 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (14312 hom., cov: 34)
  • Exomes 𝑓: 0.24 (9 hom.)
• Consequence: NFATC1 ENST00000427363.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFATC1	NM_001278669.2	c.*1229T>C		3_prime_UTR_variant	10/10	ENST00000427363.7	NP_001265598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFATC1	ENST00000427363.7	c.*1229T>C		3_prime_UTR_variant	10/10	1	NM_001278669.2	ENSP00000389377	P4

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53364 AN: 152050 Hom.: 14261 Cov.: 34

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.235 AC: 63 AN: 268 Hom.: 9 Cov.: 0 AF XY: 0.253 AC XY: 39 AN XY: 154

Gnomad4 FIN exome AF: 0.231

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.352 AC: 53491 AN: 152168 Hom.: 14312 Cov.: 34 AF XY: 0.343 AC XY: 25502 AN XY: 74396

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.0766

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.290

Alfa AF: 0.201 Hom.: 6652

Bravo AF: 0.379

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.55

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: rs9518; hg19: chr18-77288806;