7-93434594-GAA-GAAA

Variant names:

• chr7-93434594-G-GA
• rs74532696
• NM_001742.4:c.1150-301dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001742.4(CALCR):​c.1150-301dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 146,836 control chromosomes in the GnomAD database, including 41 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.015 (41 hom., cov: 22)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868
• Publications: 0 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0154 (2262/146836) while in subpopulation AFR AF = 0.0447 (1793/40122). AF 95% confidence interval is 0.043. There are 41 homozygotes in GnomAd4. There are 1120 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	NM_001742.4	MANE Select	c.1150-301dupT		intron	N/A	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.1198-301dupT		intron	N/A	NP_001158209.2	A0A0A0MSQ7
	CALCR	NM_001164738.2		c.1150-301dupT		intron	N/A	NP_001158210.1	P30988-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCR	ENST00000426151.7	TSL:1 MANE Select	c.1150-301_1150-300insT		intron	N/A	ENSP00000389295.1	P30988-2
	CALCR	ENST00000394441.5	TSL:1	c.1150-301_1150-300insT		intron	N/A	ENSP00000377959.1	P30988-2
	CALCR	ENST00000415529.2	TSL:1	n.*375-301_*375-300insT		intron	N/A	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2259 AN: 146776 Hom.: 41 Cov.: 22

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.00615

Gnomad EAS AF: 0.00237

Gnomad SAS AF: 0.00837

Gnomad FIN AF: 0.00173

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.00216

Gnomad OTH AF: 0.0150

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

GnomAD4 genome AF: 0.0154 AC: 2262 AN: 146836 Hom.: 41 Cov.: 22 AF XY: 0.0157 AC XY: 1120 AN XY: 71400

African (AFR) AF: 0.0447 AC: 1793 AN: 40122

American (AMR) AF: 0.0133 AC: 198 AN: 14838

Ashkenazi Jewish (ASJ) AF: 0.00615 AC: 21 AN: 3414

East Asian (EAS) AF: 0.00238 AC: 12 AN: 5052

South Asian (SAS) AF: 0.00861 AC: 40 AN: 4644

European-Finnish (FIN) AF: 0.00173 AC: 16 AN: 9258

Middle Eastern (MID) AF: 0.0319 AC: 9 AN: 282

European-Non Finnish (NFE) AF: 0.00216 AC: 143 AN: 66332

Other (OTH) AF: 0.0149 AC: 30 AN: 2012

Alfa AF: 0.0000877 Hom.: 90

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism

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: rs74532696; hg19: chr7-93063906; COSMIC: COSV64011318;