Genetic Variant NFATC1:c.-7_-5dupCGC (chr18-79396207-C-CCCG) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_001278669.2(NFATC1):c.-7_-5dupCGC 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 (no stars).

Frequency

Genomes: 𝑓 0.0042 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00042 ( 2 hom. )

Consequence

NFATC1
NM_001278669.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.279

Publications

0 publications found

Variant links:

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

NFATC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 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 VariationId is 3044671.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 634 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NFATC1	NM_001278669.2	MANE Select	c.-7_-5dupCGC	5_prime_UTR	Exon 1 of 10	NP_001265598.1	O95644-1
NFATC1	NM_006162.5		c.-7_-5dupCGC	5_prime_UTR	Exon 1 of 10	NP_006153.2
NFATC1	NM_172390.3		c.-7_-5dupCGC	5_prime_UTR	Exon 1 of 8	NP_765978.1	O95644-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NFATC1	ENST00000427363.7	TSL:1 MANE Select	c.-7_-5dupCGC	5_prime_UTR	Exon 1 of 10	ENSP00000389377.2	O95644-1
NFATC1	ENST00000253506.9	TSL:1	c.-7_-5dupCGC	5_prime_UTR	Exon 1 of 10	ENSP00000253506.5	O95644-4
NFATC1	ENST00000591814.5	TSL:1	c.-7_-5dupCGC	5_prime_UTR	Exon 1 of 8	ENSP00000466194.1	O95644-2

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

635

AN:

151422

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.000435

AC:

AN:

144692

AF XY:

0.000341

show subpopulations

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 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.:

Cov.:

AF XY:

0.000372

AC XY:

243

AN XY:

654100

show subpopulations

African (AFR)

AF:

0.0143

AC:

379

AN:

26554

American (AMR)

AF:

0.000277

AC:

AN:

32444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21658

East Asian (EAS)

AF:

0.00331

AC:

AN:

27802

South Asian (SAS)

AF:

0.0000406

AC:

AN:

73812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46256

Middle Eastern (MID)

AF:

0.000745

AC:

AN:

4028

European-Non Finnish (NFE)

AF:

0.0000193

AC:

AN:

1034076

Other (OTH)

AF:

0.000844

AC:

AN:

52112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00418

AC:

634

AN:

151530

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

289

AN XY:

74070

show subpopulations

African (AFR)

AF:

0.0147

AC:

608

AN:

41458

American (AMR)

AF:

0.00125

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000779

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67748

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000238

Hom.:

Asia WGS

AF:

0.00123

AC:

AN:

3276

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

NFATC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.28

Mutation Taster

=299/1

polymorphism

(source)

Splicing

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

Publications

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18-79396207-CCCG-CCCGCCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over