7-93435880-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001742.4(CALCR):c.1149+72A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 596,124 control chromosomes in the GnomAD database, including 7,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1450 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6331 hom.)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.526

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-93435880-T-C is Benign according to our data. Variant chr7-93435880-T-C is described in ClinVar as [Benign]. Clinvar id is 1274911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.1149+72A>G		intron_variant		ENST00000426151.7
CALCR	NM_001164737.3	c.1197+72A>G		intron_variant
CALCR	NM_001164738.2	c.1149+72A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.1149+72A>G		intron_variant		1	NM_001742.4	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17147 AN: 151802 Hom.: 1453 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0731

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.137 AC: 60787 AN: 444206 Hom.: 6331 AF XY: 0.137 AC XY: 32063 AN XY: 234188

Gnomad4 AFR exome AF: 0.0585

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.0727

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.113 AC: 17138 AN: 151918 Hom.: 1450 Cov.: 32 AF XY: 0.117 AC XY: 8678 AN XY: 74258

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.0731

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.139

Alfa AF: 0.101 Hom.: 123

Bravo AF: 0.117

Asia WGS AF: 0.296 AC: 1029 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	10
Dann	Benign	0.80

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: rs16868394; hg19: chr7-93065192; COSMIC: COSV64008366;