7-2930055-T-A

Position:

• chr7-2930055-T-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_032415.7(CARD11):​c.1590A>T​(p.Glu530Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: CARD11 NM_032415.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

Genes affected

CARD11 (HGNC:16393): (caspase recruitment domain family member 11) The protein encoded by this gene belongs to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. This protein is also a member of the CARD protein family, which is defined by carrying a characteristic caspase-associated recruitment domain (CARD). This protein has a domain structure similar to that of CARD14 protein. The CARD domains of both proteins have been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. When expressed in cells, this protein activated NF-kappaB and induced the phosphorylation of BCL10. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CARD11. . Gene score misZ 3.5439 (greater than the threshold 3.09). Trascript score misZ 3.7177 (greater than threshold 3.09). GenCC has associacion of gene with BENTA disease, immunodeficiency 11b with atopic dermatitis, severe combined immunodeficiency due to CARD11 deficiency.
• BP4: Computational evidence support a benign effect (MetaRNN=0.022274822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD11	NM_032415.7	c.1590A>T	p.Glu530Asp	missense_variant	12/25	ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3	c.1590A>T	p.Glu530Asp	missense_variant	13/26		NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD11	ENST00000396946.9	c.1590A>T	p.Glu530Asp	missense_variant	12/25	1	NM_032415.7	ENSP00000380150	P1
CARD11	ENST00000355508.3	c.6A>T	p.Glu2Asp	missense_variant	1/7	3		ENSP00000347695
CARD11	ENST00000698637.1	n.1916A>T		non_coding_transcript_exon_variant	12/24

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74286

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.050
DANN	Benign	0.32
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.022	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.6	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.26	N;N
REVEL	Benign	0.011
Sift	Benign	0.89	T;T
Sift4G	Benign	0.92	T;.
Polyphen		0.0	B;.
Vest4		0.089
MutPred		0.092		Gain of helix (P = 0.0696);.;
MVP		0.28
MPC		0.40
ClinPred		0.020	T
GERP RS		-5.4
Varity_R		0.023
gMVP		0.14

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: rs41515445; hg19: chr7-2969689;