7-93426338-G-A

Position:

• chr7-93426338-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001742.4(CALCR):​c.*18C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,354,322 control chromosomes in the GnomAD database, including 13,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1366 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12108 hom.)
• Consequence: CALCR NM_001742.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.438

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-93426338-G-A is Benign according to our data. Variant chr7-93426338-G-A is described in ClinVar as [Benign]. Clinvar id is 1230521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCR	NM_001742.4	c.*18C>T		3_prime_UTR_variant	14/14	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.*18C>T		3_prime_UTR_variant	16/16		NP_001158209.2
CALCR	NM_001164738.2	c.*18C>T		3_prime_UTR_variant	13/13		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.*18C>T		3_prime_UTR_variant	14/14	1	NM_001742.4	ENSP00000389295	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16983 AN: 151988 Hom.: 1369 Cov.: 32

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.139

GnomAD3 exomes AF: 0.148 AC: 36990 AN: 250740 Hom.: 3719 AF XY: 0.149 AC XY: 20153 AN XY: 135476

Gnomad AFR exome AF: 0.0553

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.416

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.0733

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.124 AC: 148923 AN: 1202216 Hom.: 12108 Cov.: 17 AF XY: 0.126 AC XY: 77059 AN XY: 610472

Gnomad4 AFR exome AF: 0.0589

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.0740

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.112 AC: 16975 AN: 152106 Hom.: 1366 Cov.: 32 AF XY: 0.115 AC XY: 8575 AN XY: 74350

Gnomad4 AFR AF: 0.0573

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0746

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.138

Alfa AF: 0.117 Hom.: 2034

Bravo AF: 0.115

Asia WGS AF: 0.282 AC: 979 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.78

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: rs1042138; hg19: chr7-93055650;