NM_001742.4:c.522-1523G>A

Variant names:

• chr7-93462470-C-T
• rs10488541
• NM_001742.4:c.522-1523G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

CALCR Gene-Disease associations (from GenCC):

• osteoporosis

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.522-1523G>A		intron_variant	Intron 7 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.522-360G>A		intron_variant	Intron 8 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.522-1523G>A		intron_variant	Intron 6 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.522-1523G>A		intron_variant	Intron 7 of 13	1	NM_001742.4	ENSP00000389295.1

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

African (AFR) AF: 0.280 AC: 11622 AN: 41478

American (AMR) AF: 0.332 AC: 5061 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1708 AN: 3468

East Asian (EAS) AF: 0.405 AC: 2086 AN: 5146

South Asian (SAS) AF: 0.487 AC: 2346 AN: 4822

European-Finnish (FIN) AF: 0.404 AC: 4256 AN: 10542

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.480 AC: 32605 AN: 67900

Other (OTH) AF: 0.423 AC: 893 AN: 2110

Alfa AF: 0.429 Hom.: 1883

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
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

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: rs10488541; hg19: chr7-93091782;