NM_001742.4:c.-27+1699G>A

Variant names:

• chr7-93572590-C-T
• rs10237272
• NM_001742.4:c.-27+1699G>A

Variant summary

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

The NM_001742.4(CALCR):​c.-27+1699G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,954 control chromosomes in the GnomAD database, including 31,262 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 0.62 (31262 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.-27+1699G>A		intron_variant	Intron 2 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.-98+1699G>A		intron_variant	Intron 2 of 15		NP_001158209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.-27+1699G>A		intron_variant	Intron 2 of 13	1	NM_001742.4	ENSP00000389295.1
CALCR	ENST00000649521.1	c.-98+1699G>A		intron_variant	Intron 1 of 14			ENSP00000497687.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94576 AN: 151836 Hom.: 31213 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.623 AC: 94683 AN: 151954 Hom.: 31262 Cov.: 32 AF XY: 0.617 AC XY: 45781 AN XY: 74232

African (AFR) AF: 0.857 AC: 35564 AN: 41504

American (AMR) AF: 0.545 AC: 8318 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2026 AN: 3462

East Asian (EAS) AF: 0.691 AC: 3567 AN: 5160

South Asian (SAS) AF: 0.637 AC: 3069 AN: 4818

European-Finnish (FIN) AF: 0.427 AC: 4495 AN: 10522

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35700 AN: 67894

Other (OTH) AF: 0.591 AC: 1250 AN: 2114

Alfa AF: 0.564 Hom.: 65890

Bravo AF: 0.640

Asia WGS AF: 0.671 AC: 2334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10237272; hg19: chr7-93201902;