rs9518

Variant names:

• chr18-79528806-T-C
• rs9518
• NM_001278669.2:c.*1229T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278669.2(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 NM_001278669.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 17 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 -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.

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.*1229T>C		3_prime_UTR	Exon 10 of 10	NP_001265598.1	O95644-1
	NFATC1	NM_172387.3		c.*1229T>C		3_prime_UTR	Exon 10 of 10	NP_765975.1	O95644-6
	NFATC1	NM_006162.5		c.*1276T>C		3_prime_UTR	Exon 10 of 10	NP_006153.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	ENST00000427363.7	TSL:1 MANE Select	c.*1229T>C		3_prime_UTR	Exon 10 of 10	ENSP00000389377.2	O95644-1
	NFATC1	ENST00000329101.8	TSL:1	c.*1229T>C		3_prime_UTR	Exon 10 of 10	ENSP00000327850.3	O95644-6
	NFATC1	ENST00000253506.9	TSL:1	c.*1276T>C		3_prime_UTR	Exon 10 of 10	ENSP00000253506.5	O95644-4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.231 AC: 61 AN: 264

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.756 AC: 31387 AN: 41496

American (AMR) AF: 0.288 AC: 4410 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 266 AN: 3472

East Asian (EAS) AF: 0.171 AC: 885 AN: 5182

South Asian (SAS) AF: 0.133 AC: 641 AN: 4828

European-Finnish (FIN) AF: 0.181 AC: 1919 AN: 10584

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13249 AN: 68004

Other (OTH) AF: 0.290 AC: 612 AN: 2110

Alfa AF: 0.224 Hom.: 13408

Bravo AF: 0.379

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.55
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs9518; hg19: chr18-77288806;