NM_004554.5:c.2056+95G>T

Variant names:

• chr14-24376196-G-T
• rs10141896
• NM_004554.5:c.2056+95G>T

Variant summary

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

The NM_004554.5(NFATC4):​c.2056+95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,589,074 control chromosomes in the GnomAD database, including 3,126 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 0.045 (340 hom., cov: 31)
  • Exomes 𝑓: 0.042 (2786 hom.)
• Consequence: NFATC4 NM_004554.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 10 publications found

Genes affected

NFATC4 (HGNC:7778): (nuclear factor of activated T cells 4) This gene encodes a member of the nuclear factor of activated T cells (NFAT) protein family. The encoded protein is part of a 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 stimulation and an inducible nuclear component. NFAT proteins are activated by the calmodulin-dependent phosphatase, calcineurin. The encoded protein plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of interleukin-2 and interleukin-4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004554.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC4	NM_004554.5	MANE Select	c.2056+95G>T		intron	N/A	NP_004545.2
	NFATC4	NM_001320043.2		c.2245+95G>T		intron	N/A	NP_001306972.1
	NFATC4	NM_001136022.3		c.2245+95G>T		intron	N/A	NP_001129494.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC4	ENST00000250373.9	TSL:1 MANE Select	c.2056+95G>T		intron	N/A	ENSP00000250373.4
	NFATC4	ENST00000413692.6	TSL:1	c.2245+95G>T		intron	N/A	ENSP00000388910.2
	NFATC4	ENST00000556279.5	TSL:1	c.2152+95G>T		intron	N/A	ENSP00000452270.1

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6837 AN: 152038 Hom.: 341 Cov.: 31

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0316

GnomAD4 exome AF: 0.0417 AC: 59895 AN: 1436918 Hom.: 2786 Cov.: 34 AF XY: 0.0443 AC XY: 31509 AN XY: 711876

African (AFR) AF: 0.0418 AC: 1376 AN: 32942

American (AMR) AF: 0.0414 AC: 1779 AN: 42968

Ashkenazi Jewish (ASJ) AF: 0.0149 AC: 363 AN: 24384

East Asian (EAS) AF: 0.244 AC: 9604 AN: 39420

South Asian (SAS) AF: 0.137 AC: 11274 AN: 82092

European-Finnish (FIN) AF: 0.0568 AC: 2968 AN: 52272

Middle Eastern (MID) AF: 0.0163 AC: 92 AN: 5628

European-Non Finnish (NFE) AF: 0.0269 AC: 29512 AN: 1097980

Other (OTH) AF: 0.0494 AC: 2927 AN: 59232

GnomAD4 genome AF: 0.0449 AC: 6831 AN: 152156 Hom.: 340 Cov.: 31 AF XY: 0.0494 AC XY: 3677 AN XY: 74392

African (AFR) AF: 0.0430 AC: 1784 AN: 41504

American (AMR) AF: 0.0322 AC: 493 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.264 AC: 1362 AN: 5164

South Asian (SAS) AF: 0.148 AC: 711 AN: 4814

European-Finnish (FIN) AF: 0.0567 AC: 601 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0261 AC: 1772 AN: 67972

Other (OTH) AF: 0.0303 AC: 64 AN: 2110

Alfa AF: 0.0339 Hom.: 287

Bravo AF: 0.0412

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.016
DANN	Benign	0.52
PhyloP100		-2.4
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: rs10141896; hg19: chr14-24845402; COSMIC: COSV51598086; COSMIC: COSV51598086;