7-93435803-G-C

Position:

• chr7-93435803-G-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+149C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 232,476 control chromosomes in the GnomAD database, including 46,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29398 hom., cov: 26)
  • Exomes 𝑓: 0.62 (16835 hom.)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.769

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=-1.01).
• BP6: Variant 7-93435803-G-C is Benign according to our data. Variant chr7-93435803-G-C is described in ClinVar as [Benign]. Clinvar id is 1237362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.1149+149C>G		intron_variant		ENST00000426151.7
CALCR	NM_001164737.3	c.1197+149C>G		intron_variant
CALCR	NM_001164738.2	c.1149+149C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.1149+149C>G		intron_variant		1	NM_001742.4	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 92677 AN: 148452 Hom.: 29391 Cov.: 26

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.666

GnomAD4 exome AF: 0.619 AC: 51959 AN: 83920 Hom.: 16835 AF XY: 0.619 AC XY: 29007 AN XY: 46862

Gnomad4 AFR exome AF: 0.570

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.903

Gnomad4 SAS exome AF: 0.646

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.651

GnomAD4 genome AF: 0.624 AC: 92730 AN: 148556 Hom.: 29398 Cov.: 26 AF XY: 0.624 AC XY: 45109 AN XY: 72334

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.667

Alfa AF: 0.435 Hom.: 1076

Bravo AF: 0.646

Asia WGS AF: 0.780 AC: 2708 AN: 3472

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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.20

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: rs10215616; hg19: chr7-93065115;