7-93434086-G-T

Position:

• chr7-93434086-G-T

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.1191+167C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,098 control chromosomes in the GnomAD database, including 4,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.22 (4026 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.11

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=-0.8).
• BP6: Variant 7-93434086-G-T is Benign according to our data. Variant chr7-93434086-G-T is described in ClinVar as [Benign]. Clinvar id is 1224047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1191+167C>A		intron_variant		ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1239+167C>A		intron_variant			NP_001158209.2
CALCR	NM_001164738.2	c.1191+167C>A		intron_variant			NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.1191+167C>A		intron_variant		1	NM_001742.4	ENSP00000389295	P1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33030 AN: 151980 Hom.: 4020 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.217 AC: 33056 AN: 152098 Hom.: 4026 Cov.: 32 AF XY: 0.223 AC XY: 16591 AN XY: 74358

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.224

Alfa AF: 0.207 Hom.: 587

Bravo AF: 0.220

Asia WGS AF: 0.349 AC: 1211 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	-0.80
CADD	Benign	11
DANN	Benign	0.56

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: rs2072083; hg19: chr7-93063398;