rs2044750

Variant names:

• chr18-79519750-G-A
• rs2044750
• NM_001278669.2:c.2783-7778G>A

Variant summary

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

The NM_001278669.2(NFATC1):​c.2783-7778G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,008 control chromosomes in the GnomAD database, including 10,812 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 0.36 (10812 hom., cov: 32)
• Consequence: NFATC1 NM_001278669.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 6 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

LOC102723506 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 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.2783-7778G>A		intron	N/A	NP_001265598.1	O95644-1
	NFATC1	NM_172387.3		c.2744-7778G>A		intron	N/A	NP_765975.1	O95644-6
	NFATC1	NM_006162.5		c.2476-7778G>A		intron	N/A	NP_006153.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	ENST00000427363.7	TSL:1 MANE Select	c.2783-7778G>A		intron	N/A	ENSP00000389377.2	O95644-1
	NFATC1	ENST00000329101.8	TSL:1	c.2744-7778G>A		intron	N/A	ENSP00000327850.3	O95644-6
	NFATC1	ENST00000253506.9	TSL:1	c.2476-7778G>A		intron	N/A	ENSP00000253506.5	O95644-4

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55188 AN: 151890 Hom.: 10812 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.350

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.363 AC: 55191 AN: 152008 Hom.: 10812 Cov.: 32 AF XY: 0.361 AC XY: 26829 AN XY: 74290

African (AFR) AF: 0.255 AC: 10587 AN: 41454

American (AMR) AF: 0.315 AC: 4810 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1341 AN: 3472

East Asian (EAS) AF: 0.149 AC: 770 AN: 5182

South Asian (SAS) AF: 0.296 AC: 1428 AN: 4826

European-Finnish (FIN) AF: 0.499 AC: 5262 AN: 10538

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29754 AN: 67962

Other (OTH) AF: 0.346 AC: 728 AN: 2106

Alfa AF: 0.401 Hom.: 44670

Bravo AF: 0.339

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.63
PhyloP100		-2.0
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: rs2044750; hg19: chr18-77279750;