rs10488548

Positions:

• chr7-93501685-A-G

Variant summary

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

The NM_001742.4(CALCR):​c.-26-14678T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,050 control chromosomes in the GnomAD database, including 2,648 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 0.13 (2648 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.-26-14678T>C		intron_variant		ENST00000426151.7
CALCR	NM_001164737.3	c.-97-5711T>C		intron_variant
CALCR	NM_001164738.2	c.-26-14678T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.-26-14678T>C		intron_variant		1	NM_001742.4	P1
CALCR	ENST00000394441.5	c.-26-14678T>C		intron_variant		1		P1
CALCR	ENST00000649521.1	c.-97-5711T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19195 AN: 151932 Hom.: 2634 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.127 AC: 19242 AN: 152050 Hom.: 2648 Cov.: 32 AF XY: 0.128 AC XY: 9502 AN XY: 74344

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.0960

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0798 Hom.: 379

Bravo AF: 0.139

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.30

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: rs10488548; hg19: chr7-93130997;