chr7-93426338-G-A

Variant names:

• chr7-93426338-G-A
• rs1042138
• NM_001742.4:c.*18C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

CALCR Gene-Disease associations (from GenCC):

• osteoporosis

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.*18C>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.*18C>T		3_prime_UTR_variant	Exon 16 of 16		NP_001158209.2
CALCR	NM_001164738.2	c.*18C>T		3_prime_UTR_variant	Exon 13 of 13		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.*18C>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_001742.4	ENSP00000389295.1

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

GnomAD2 exomes AF: 0.148 AC: 36990 AN: 250740 AF XY: 0.149

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 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

African (AFR) AF: 0.0589 AC: 1664 AN: 28238

American (AMR) AF: 0.169 AC: 7472 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4634 AN: 24556

East Asian (EAS) AF: 0.432 AC: 16500 AN: 38226

South Asian (SAS) AF: 0.194 AC: 15672 AN: 80600

European-Finnish (FIN) AF: 0.0740 AC: 3941 AN: 53248

Middle Eastern (MID) AF: 0.206 AC: 1081 AN: 5256

European-Non Finnish (NFE) AF: 0.104 AC: 90681 AN: 876078

Other (OTH) AF: 0.141 AC: 7278 AN: 51670

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

African (AFR) AF: 0.0573 AC: 2379 AN: 41512

American (AMR) AF: 0.135 AC: 2062 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2222 AN: 5126

South Asian (SAS) AF: 0.210 AC: 1010 AN: 4814

European-Finnish (FIN) AF: 0.0746 AC: 790 AN: 10586

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7350 AN: 67998

Other (OTH) AF: 0.138 AC: 292 AN: 2110

Alfa AF: 0.114 Hom.: 4392

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1042138; hg19: chr7-93055650;