7-93434594-GAA-GAAAAA

Variant names:

• chr7-93434594-G-GAAA
• rs74532696
• NM_001742.4:c.1150-303_1150-301dupTTT

Variant summary

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

The NM_001742.4(CALCR):​c.1150-303_1150-301dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 146,944 control chromosomes in the GnomAD database, including 70 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.024 (70 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 amr. GnomAd4 allele frequency = 0.0241 (3536/146944) while in subpopulation AMR AF = 0.053 (787/14836). AF 95% confidence interval is 0.05. There are 70 homozygotes in GnomAd4. There are 1772 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 70 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1150-303_1150-301dupTTT		intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1198-303_1198-301dupTTT		intron_variant	Intron 14 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.1150-303_1150-301dupTTT		intron_variant	Intron 11 of 12		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.1150-301_1150-300insTTT		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3530 AN: 146886 Hom.: 67 Cov.: 22

Gnomad AFR AF: 0.00607

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0111

Gnomad EAS AF: 0.00158

Gnomad SAS AF: 0.00773

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0190

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

GnomAD4 genome AF: 0.0241 AC: 3536 AN: 146944 Hom.: 70 Cov.: 22 AF XY: 0.0248 AC XY: 1772 AN XY: 71460

African (AFR) AF: 0.00605 AC: 243 AN: 40154

American (AMR) AF: 0.0530 AC: 787 AN: 14836

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 38 AN: 3414

East Asian (EAS) AF: 0.00158 AC: 8 AN: 5052

South Asian (SAS) AF: 0.00775 AC: 36 AN: 4644

European-Finnish (FIN) AF: 0.0496 AC: 460 AN: 9278

Middle Eastern (MID) AF: 0.00709 AC: 2 AN: 282

European-Non Finnish (NFE) AF: 0.0285 AC: 1891 AN: 66390

Other (OTH) AF: 0.0189 AC: 38 AN: 2012

Alfa AF: 0.0111 Hom.: 90

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Other links and lift over

dbSNP: rs74532696; hg19: chr7-93063906;