rs10488551

chr7-93534407-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+39882G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,578 control chromosomes in the GnomAD database, including 7,174 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 (7174 hom., cov: 31)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.-27+39882G>A		intron_variant		ENST00000426151.7
LOC105375400	XR_927749.3	n.71+671C>T		intron_variant, non_coding_transcript_variant
CALCR	NM_001164737.3	c.-97-38433G>A		intron_variant
CALCR	NM_001164738.2	c.-27+25114G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.-27+39882G>A		intron_variant		1	NM_001742.4	P1
CALCR	ENST00000394441.5	c.-27+25114G>A		intron_variant		1		P1
CALCR	ENST00000649521.1	c.-97-38433G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42755 AN: 151460 Hom.: 7175 Cov.: 31

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.282 AC: 42751 AN: 151578 Hom.: 7174 Cov.: 31 AF XY: 0.282 AC XY: 20907 AN XY: 74084

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.308

Alfa AF: 0.365 Hom.: 20255

Bravo AF: 0.266

Asia WGS AF: 0.277 AC: 966 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.4
Dann	Benign	0.74

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: rs10488551; hg19: chr7-93163719; COSMIC: COSV64006352;