7-93426915-A-G

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.1192-326T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,266 control chromosomes in the GnomAD database, including 1,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1377 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.275

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=-0.87).
• BP6: Variant 7-93426915-A-G is Benign according to our data. Variant chr7-93426915-A-G is described in ClinVar as [Benign]. Clinvar id is 1289488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.1192-326T>C		intron_variant		ENST00000426151.7
CALCR	NM_001164737.3	c.1240-326T>C		intron_variant
CALCR	NM_001164738.2	c.1192-326T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.1192-326T>C		intron_variant		1	NM_001742.4	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17035 AN: 152148 Hom.: 1380 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: 0.435

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.112 AC: 17027 AN: 152266 Hom.: 1377 Cov.: 32 AF XY: 0.116 AC XY: 8610 AN XY: 74456

Gnomad4 AFR AF: 0.0573

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.0747

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0993 Hom.: 110

Bravo AF: 0.116

Asia WGS AF: 0.283 AC: 983 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.0
Dann	Benign	0.79

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: rs72615123; hg19: chr7-93056227;