rs12154667

Positions:

• chr7-93549490-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.-27+24799G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,876 control chromosomes in the GnomAD database, including 12,138 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 0.38 (12138 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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]

LOC105375400 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCR	NM_001742.4	c.-27+24799G>A		intron_variant		ENST00000426151.7	NP_001733.1
LOC105375400	XR_927749.3	n.72-1318C>T		intron_variant, non_coding_transcript_variant
CALCR	NM_001164737.3	c.-98+24799G>A		intron_variant			NP_001158209.2
CALCR	NM_001164738.2	c.-27+10031G>A		intron_variant			NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.-27+24799G>A		intron_variant		1	NM_001742.4	ENSP00000389295	P1
CALCR	ENST00000394441.5	c.-27+10031G>A		intron_variant		1		ENSP00000377959	P1
CALCR	ENST00000649521.1	c.-98+24799G>A		intron_variant				ENSP00000497687

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57782 AN: 151758 Hom.: 12136 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.381 AC: 57799 AN: 151876 Hom.: 12138 Cov.: 32 AF XY: 0.377 AC XY: 28003 AN XY: 74218

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.418

Alfa AF: 0.411 Hom.: 1721

Bravo AF: 0.368

Asia WGS AF: 0.359 AC: 1246 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.25

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: rs12154667; hg19: chr7-93178802;