7-93434389-GAAAAA-GA

Variant names:

• chr7-93434389-GAAAA-G
• rs200558502
• NM_001742.4:c.1150-99_1150-96delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001742.4(CALCR):​c.1150-99_1150-96delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 376,376 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: not found (cov: 0)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1150-99_1150-96delTTTT		intron	N/A	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.1198-99_1198-96delTTTT		intron	N/A	NP_001158209.2	A0A0A0MSQ7
	CALCR	NM_001164738.2		c.1150-99_1150-96delTTTT		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.1150-99_1150-96delTTTT		intron	N/A	ENSP00000389295.1	P30988-2
	CALCR	ENST00000394441.5	TSL:1	c.1150-99_1150-96delTTTT		intron	N/A	ENSP00000377959.1	P30988-2
	CALCR	ENST00000415529.2	TSL:1	n.*375-99_*375-96delTTTT		intron	N/A	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000106 AC: 4 AN: 376376 Hom.: 0 AF XY: 0.0000100 AC XY: 2 AN XY: 199236

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

African (AFR) AF: 0.00 AC: 0 AN: 10886

American (AMR) AF: 0.00 AC: 0 AN: 15874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12494

East Asian (EAS) AF: 0.00 AC: 0 AN: 26252

South Asian (SAS) AF: 0.00 AC: 0 AN: 29426

European-Finnish (FIN) AF: 0.0000355 AC: 1 AN: 28154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2082

European-Non Finnish (NFE) AF: 0.0000131 AC: 3 AN: 229358

Other (OTH) AF: 0.00 AC: 0 AN: 21850

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;