11-830670-G-A

Variant names:

• chr11-830670-G-A
• rs4075289
• NM_001286606.2:c.743G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286606.2(CRACR2B):​c.743G>A​(p.Ser248Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 35)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CRACR2B NM_001286606.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053962797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRACR2B	NM_001286606.2	c.743G>A	p.Ser248Asn	missense_variant	Exon 6 of 9	ENST00000525077.2	NP_001273535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRACR2B	ENST00000525077.2	c.743G>A	p.Ser248Asn	missense_variant	Exon 6 of 9	1	NM_001286606.2	ENSP00000435299.1
CRACR2B	ENST00000528542.6	c.743G>A	p.Ser248Asn	missense_variant	Exon 7 of 9	1		ENSP00000432334.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394160 Hom.: 0 Cov.: 97 AF XY: 0.00000145 AC XY: 1 AN XY: 687432

African (AFR) AF: 0.00 AC: 0 AN: 31506

American (AMR) AF: 0.00 AC: 0 AN: 35618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25122

East Asian (EAS) AF: 0.00 AC: 0 AN: 35676

South Asian (SAS) AF: 0.00 AC: 0 AN: 79060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4702

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077904

Other (OTH) AF: 0.00 AC: 0 AN: 57800

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.029	.;.;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.50	.;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L;L;L
PhyloP100		0.30
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.034
Sift	Benign	0.35	T;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.055
MutPred		0.16		Loss of phosphorylation at S248 (P = 0.0093);Loss of phosphorylation at S248 (P = 0.0093);Loss of phosphorylation at S248 (P = 0.0093);
MVP		0.11
MPC		0.027
ClinPred		0.097	T
GERP RS		1.0
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.072
gMVP		0.041
Mutation Taster		=95/5	polymorphism

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: rs4075289; hg19: chr11-830670;