rs753549408

Variant names:

• chr11-828698-C-A
• NM_001286606.2:c.91C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-828698-C-A
• chr11-828698-C-G

Variant summary

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

The NM_001286606.2(CRACR2B):​c.91C>A​(p.Leu31Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. L31P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRACR2B NM_001286606.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

Genes affected

CRACR2B (HGNC:28703): (calcium release activated channel regulator 2B) Predicted to enable calcium ion binding activity. Involved in store-operated calcium entry. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255108 (HGNC:):

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=0.16267276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRACR2B	NM_001286606.2	c.91C>A	p.Leu31Met	missense_variant	Exon 1 of 9	ENST00000525077.2	NP_001273535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRACR2B	ENST00000525077.2	c.91C>A	p.Leu31Met	missense_variant	Exon 1 of 9	1	NM_001286606.2	ENSP00000435299.1
CRACR2B	ENST00000528542.6	c.91C>A	p.Leu31Met	missense_variant	Exon 2 of 9	1		ENSP00000432334.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460236 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726512

Gnomad4 AFR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T;.;.;.;.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.44	T;T;T;T;.;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	.;.;.;.;M;M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.095	.;T;T;D;T;T;T
Sift4G	Pathogenic	0.0	D;T;T;D;T;T;T
Polyphen		0.48, 0.87	.;.;.;.;P;P;P
Vest4		0.24, 0.30
MutPred		0.20		Gain of catalytic residue at L31 (P = 0.1493);Gain of catalytic residue at L31 (P = 0.1493);Gain of catalytic residue at L31 (P = 0.1493);Gain of catalytic residue at L31 (P = 0.1493);Gain of catalytic residue at L31 (P = 0.1493);Gain of catalytic residue at L31 (P = 0.1493);Gain of catalytic residue at L31 (P = 0.1493);
MVP		0.25
MPC		0.073
ClinPred		0.64	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-828698;