rs372607625

Variant names:

• chr11-67519910-C-G
• NM_016366.3:c.520G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-67519910-C-G
• chr11-67519910-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016366.3(CABP2):​c.520G>C​(p.Val174Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V174M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CABP2 NM_016366.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01

Genes affected

CABP2 (HGNC:1385): (calcium binding protein 2) This gene belongs to a subfamily of calcium binding proteins that share similarity to calmodulin. Like calmodulin, these family members can likely stimulate calmodulin-dependent kinase II and the protein phosphatase calcineurin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08896893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABP2	NM_016366.3	c.520G>C	p.Val174Leu	missense_variant	Exon 6 of 7	ENST00000294288.5	NP_057450.2
CABP2	NM_001318496.2	c.538G>C	p.Val180Leu	missense_variant	Exon 6 of 7		NP_001305425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP2	ENST00000294288.5	c.520G>C	p.Val174Leu	missense_variant	Exon 6 of 7	1	NM_016366.3	ENSP00000294288.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458764 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725780

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.023
DANN	Benign	0.86
DEOGEN2	Benign	0.048	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.85	.;L;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.28	N;N;.
REVEL	Benign	0.081
Sift	Benign	0.27	T;T;.
Sift4G	Benign	0.36	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.12
MutPred		0.48		.;Gain of disorder (P = 0.1181);.;
MVP		0.51
MPC		0.27
ClinPred		0.10	T
GERP RS		-3.2
Varity_R		0.042
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-67287381;