chr11-829393-C-T

Variant names:

• chr11-829393-C-T
• rs200792273
• NM_001286606.2:c.311C>T

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.311C>T​(p.Ala104Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,782 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A104E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CRACR2B NM_001286606.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864
• Publications: 1 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=0.056773007).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286606.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACR2B	NM_001286606.2	MANE Select	c.311C>T	p.Ala104Val	missense	Exon 3 of 9	NP_001273535.1	Q8N4Y2-1
	CRACR2B	NM_173584.4		c.311C>T	p.Ala104Val	missense	Exon 3 of 8	NP_775855.3	Q8N4Y2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACR2B	ENST00000525077.2	TSL:1 MANE Select	c.311C>T	p.Ala104Val	missense	Exon 3 of 9	ENSP00000435299.1	Q8N4Y2-1
	CRACR2B	ENST00000450448.5	TSL:1	c.311C>T	p.Ala104Val	missense	Exon 3 of 8	ENSP00000409256.1	Q8N4Y2-3
	CRACR2B	ENST00000528542.6	TSL:1	c.311C>T	p.Ala104Val	missense	Exon 4 of 9	ENSP00000432334.1	Q8N4Y2-3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457782 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725078

African (AFR) AF: 0.00 AC: 0 AN: 33300

American (AMR) AF: 0.00 AC: 0 AN: 43916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 85718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110976

Other (OTH) AF: 0.00 AC: 0 AN: 60252

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.86
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.0070
Sift	Benign	0.13	T
Sift4G	Benign	0.39	T
Polyphen		0.12	B
Vest4		0.090
MutPred		0.23		Loss of disorder (P = 0.0934)
MVP		0.15
MPC		0.028
ClinPred		0.049	T
GERP RS		-2.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.058
gMVP		0.19
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs200792273; hg19: chr11-829393;