rs1028982369

Variant names:

• chr7-128748365-C-G
• rs1028982369
• ENST00000479257.5:c.11C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-128748365-C-G
• chr7-128748365-C-A
• chr7-128748365-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199671.2(CALU):​c.11C>G​(p.Thr4Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000333 in 1,501,760 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: CALU NM_001199671.2 missense, splice_region
• Scores: Splicing: ADA: 0.07049
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.613
• Publications: 0 publications found

Genes affected

CALU (HGNC:1458): (calumenin) The product of this gene is a calcium-binding protein localized in the endoplasmic reticulum (ER) and it is involved in such ER functions as protein folding and sorting. This protein belongs to a family of multiple EF-hand proteins (CERC) that include reticulocalbin, ERC-55, and Cab45 and the product of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08974671).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199671.2. 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
	CALU	NM_001219.5	MANE Select	c.-11-208C>G		intron	N/A	NP_001210.1	Q6IAW5
	CALU	NM_001199671.2		c.11C>G	p.Thr4Ser	missense splice_region	Exon 2 of 8	NP_001186600.1	O43852-3
	CALU	NM_001199672.2		c.11C>G	p.Thr4Ser	missense splice_region	Exon 2 of 8	NP_001186601.1	O43852-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALU	ENST00000479257.5	TSL:1	c.11C>G	p.Thr4Ser	missense splice_region	Exon 2 of 8	ENSP00000420381.1	O43852-3
	CALU	ENST00000542996.7	TSL:1	c.11C>G	p.Thr4Ser	missense splice_region	Exon 2 of 8	ENSP00000438248.1	O43852-4
	CALU	ENST00000249364.9	TSL:1 MANE Select	c.-11-208C>G		intron	N/A	ENSP00000249364.4	O43852-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000296 AC: 4 AN: 1349608 Hom.: 0 Cov.: 24 AF XY: 0.00000300 AC XY: 2 AN XY: 666694

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30492

American (AMR) AF: 0.00 AC: 0 AN: 32716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24630

East Asian (EAS) AF: 0.00 AC: 0 AN: 35500

South Asian (SAS) AF: 0.00 AC: 0 AN: 74548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5598

European-Non Finnish (NFE) AF: 0.00000284 AC: 3 AN: 1055608

Other (OTH) AF: 0.0000176 AC: 1 AN: 56722

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00955443), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.52
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.61
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.045
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.047
MutPred		0.22		Gain of ubiquitination at K2 (P = 0.0554)
MVP		0.25
MPC		0.29
ClinPred		0.037	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.18
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.070
dbscSNV1_RF	Benign	0.16
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: rs1028982369; hg19: chr7-128388419;