chr7-93471768-T-C

Variant names:

• chr7-93471768-T-C
• rs10250228
• NM_001742.4:c.429+607A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001742.4(CALCR):​c.429+607A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,518 control chromosomes in the GnomAD database, including 16,621 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16621 hom., cov: 31)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.429+607A>G		intron_variant	Intron 6 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.429+607A>G		intron_variant	Intron 7 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.429+607A>G		intron_variant	Intron 5 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.429+607A>G		intron_variant	Intron 6 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70364 AN: 151400 Hom.: 16598 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.465 AC: 70423 AN: 151518 Hom.: 16621 Cov.: 31 AF XY: 0.459 AC XY: 33983 AN XY: 74000

African (AFR) AF: 0.487 AC: 20143 AN: 41388

American (AMR) AF: 0.355 AC: 5387 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1707 AN: 3460

East Asian (EAS) AF: 0.405 AC: 2070 AN: 5106

South Asian (SAS) AF: 0.556 AC: 2671 AN: 4806

European-Finnish (FIN) AF: 0.404 AC: 4261 AN: 10558

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32572 AN: 67726

Other (OTH) AF: 0.469 AC: 986 AN: 2104

Alfa AF: 0.474 Hom.: 45432

Bravo AF: 0.457

Asia WGS AF: 0.430 AC: 1497 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.26
DANN	Benign	0.34
PhyloP100		-1.4
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: rs10250228; hg19: chr7-93101080;