rs10488541

Positions:

• chr7-93462470-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001742.4(CALCR):​c.522-1523G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,932 control chromosomes in the GnomAD database, including 13,022 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13022 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912

Genes affected

CALCR (HGNC:1440): (calcitonin receptor) This gene encodes a high affinity receptor for the peptide hormone calcitonin and belongs to a subfamily of seven transmembrane-spanning G protein-coupled receptors. The encoded protein is involved in maintaining calcium homeostasis and in regulating osteoclast-mediated bone resorption. Polymorphisms in this gene have been associated with variations in bone mineral density and onset of osteoporosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.522-1523G>A		intron_variant		ENST00000426151.7
CALCR	NM_001164737.3	c.522-360G>A		intron_variant
CALCR	NM_001164738.2	c.522-1523G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.522-1523G>A		intron_variant		1	NM_001742.4	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61176 AN: 151816 Hom.: 13017 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.420

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.403 AC: 61198 AN: 151932 Hom.: 13022 Cov.: 32 AF XY: 0.398 AC XY: 29521 AN XY: 74220

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.423

Alfa AF: 0.436 Hom.: 1858

Bravo AF: 0.389

Asia WGS AF: 0.386 AC: 1341 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs10488541; hg19: chr7-93091782;