chr7-93432102-C-T

Variant names:

• chr7-93432102-C-T
• rs13232226
• NM_001742.4:c.1191+2151G>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.1191+2151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,026 control chromosomes in the GnomAD database, including 5,269 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 0.26 (5269 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1191+2151G>A		intron_variant	Intron 13 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1239+2151G>A		intron_variant	Intron 15 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.1191+2151G>A		intron_variant	Intron 12 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.1191+2151G>A		intron_variant	Intron 13 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38810 AN: 151910 Hom.: 5272 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.0288

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.255 AC: 38826 AN: 152026 Hom.: 5269 Cov.: 32 AF XY: 0.247 AC XY: 18382 AN XY: 74328

African (AFR) AF: 0.265 AC: 10994 AN: 41416

American (AMR) AF: 0.254 AC: 3874 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3470

East Asian (EAS) AF: 0.0287 AC: 149 AN: 5190

South Asian (SAS) AF: 0.186 AC: 898 AN: 4828

European-Finnish (FIN) AF: 0.160 AC: 1691 AN: 10582

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19144 AN: 67944

Other (OTH) AF: 0.285 AC: 601 AN: 2112

Alfa AF: 0.228 Hom.: 1571

Bravo AF: 0.264

Asia WGS AF: 0.136 AC: 476 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		0.18
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: rs13232226; hg19: chr7-93061414;