rs10488554

chr7-93553003-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+21286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,058 control chromosomes in the GnomAD database, including 7,191 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 0.28 (7191 hom., cov: 33)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.-27+21286G>A		intron_variant		ENST00000426151.7
LOC105375400	XR_927749.3	n.200+2067C>T		intron_variant, non_coding_transcript_variant
CALCR	NM_001164737.3	c.-98+21286G>A		intron_variant
CALCR	NM_001164738.2	c.-27+6518G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.-27+21286G>A		intron_variant		1	NM_001742.4	P1
CALCR	ENST00000394441.5	c.-27+6518G>A		intron_variant		1		P1
CALCR	ENST00000649521.1	c.-98+21286G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42537 AN: 151942 Hom.: 7193 Cov.: 33

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.280 AC: 42531 AN: 152058 Hom.: 7191 Cov.: 33 AF XY: 0.280 AC XY: 20795 AN XY: 74304

Gnomad4 AFR AF: 0.0825

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.307

Alfa AF: 0.297 Hom.: 1122

Bravo AF: 0.262

Asia WGS AF: 0.278 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.1
Dann	Benign	0.75

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: rs10488554; hg19: chr7-93182315;