7-93434389-GAAAAA-GAAA

Variant names:

• chr7-93434389-GAA-G
• rs200558502
• NM_001742.4:c.1150-97_1150-96delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001742.4(CALCR):​c.1150-97_1150-96delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 507,668 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000074 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1150-97_1150-96delTT		intron_variant	Intron 12 of 13	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1198-97_1198-96delTT		intron_variant	Intron 14 of 15		NP_001158209.2
CALCR	NM_001164738.2	c.1150-97_1150-96delTT		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.1150-97_1150-96delTT		intron_variant	Intron 12 of 13	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes AF: 0.00000737 AC: 1 AN: 135618 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000140

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00178 AC: 661 AN: 372050 Hom.: 0 AF XY: 0.00190 AC XY: 374 AN XY: 197056

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00158 AC: 17 AN: 10778

American (AMR) AF: 0.00146 AC: 23 AN: 15774

Ashkenazi Jewish (ASJ) AF: 0.00178 AC: 22 AN: 12360

East Asian (EAS) AF: 0.000191 AC: 5 AN: 26156

South Asian (SAS) AF: 0.00303 AC: 88 AN: 29052

European-Finnish (FIN) AF: 0.00209 AC: 58 AN: 27792

Middle Eastern (MID) AF: 0.000484 AC: 1 AN: 2068

European-Non Finnish (NFE) AF: 0.00179 AC: 406 AN: 226452

Other (OTH) AF: 0.00190 AC: 41 AN: 21618

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000737 AC: 1 AN: 135618 Hom.: 0 Cov.: 0 AF XY: 0.0000153 AC XY: 1 AN XY: 65228

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 37228

American (AMR) AF: 0.00 AC: 0 AN: 13630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3204

East Asian (EAS) AF: 0.00 AC: 0 AN: 4926

South Asian (SAS) AF: 0.00 AC: 0 AN: 4324

European-Finnish (FIN) AF: 0.000140 AC: 1 AN: 7124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62214

Other (OTH) AF: 0.00 AC: 0 AN: 1852

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66

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: rs200558502; hg19: chr7-93063701;