7-93525996-G-C

Position:

• chr7-93525996-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001742.4(CALCR):​c.-26-38989C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,016 control chromosomes in the GnomAD database, including 7,106 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 0.28 (7106 hom., cov: 32)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCR	NM_001742.4	c.-26-38989C>G		intron_variant		ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.-97-30022C>G		intron_variant			NP_001158209.2
CALCR	NM_001164738.2	c.-27+33525C>G		intron_variant			NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.-26-38989C>G		intron_variant		1	NM_001742.4	ENSP00000389295.1
CALCR	ENST00000394441.5	c.-27+33525C>G		intron_variant		1		ENSP00000377959.1
CALCR	ENST00000649521.1	c.-97-30022C>G		intron_variant				ENSP00000497687.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42606 AN: 151896 Hom.: 7106 Cov.: 32

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.280 AC: 42606 AN: 152016 Hom.: 7106 Cov.: 32 AF XY: 0.280 AC XY: 20809 AN XY: 74304

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.308

Alfa AF: 0.191 Hom.: 477

Bravo AF: 0.264

Asia WGS AF: 0.275 AC: 959 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.4
DANN	Benign	0.67

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: rs10488550; hg19: chr7-93155308;