rs6976450

chr7-93450426-T-Cchr7-93450426-T-G

Variant summary

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

The NM_001742.4(CALCR):c.649-6669A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,002 control chromosomes in the GnomAD database, including 2,901 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 0.17 (2901 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.649-6669A>G		intron_variant		ENST00000426151.7
CALCR	NM_001164737.3	c.697-6669A>G		intron_variant
CALCR	NM_001164738.2	c.649-6669A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.649-6669A>G		intron_variant		1	NM_001742.4	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26456 AN: 151884 Hom.: 2909 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.174 AC: 26438 AN: 152002 Hom.: 2901 Cov.: 32 AF XY: 0.179 AC XY: 13319 AN XY: 74314

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.172

Alfa AF: 0.208 Hom.: 4962

Bravo AF: 0.160

Asia WGS AF: 0.304 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.71

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: rs6976450; hg19: chr7-93079738;