7-93434389-GAAAAA-GAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001742.4(CALCR):​c.1150-97_1150-96dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 502,452 control chromosomes in the GnomAD database, including 2,348 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1990 hom., cov: 0)
  • Exomes 𝑓: 0.14 (358 hom.)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.590
• 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 -10 ACMG points.

• BP6: Variant 7-93434389-G-GAA is Benign according to our data. Variant chr7-93434389-G-GAA is described in ClinVar as Benign. ClinVar VariationId is 1274232.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

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.1150-97_1150-96dupTT		intron	N/A	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.1198-97_1198-96dupTT		intron	N/A	NP_001158209.2	A0A0A0MSQ7
	CALCR	NM_001164738.2		c.1150-97_1150-96dupTT		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.1150-96_1150-95insTT		intron	N/A	ENSP00000389295.1	P30988-2
	CALCR	ENST00000394441.5	TSL:1	c.1150-96_1150-95insTT		intron	N/A	ENSP00000377959.1	P30988-2
	CALCR	ENST00000415529.2	TSL:1	n.*375-96_*375-95insTT		intron	N/A	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 22049 AN: 135296 Hom.: 1985 Cov.: 0

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.145 AC: 53079 AN: 367116 Hom.: 358 AF XY: 0.145 AC XY: 28131 AN XY: 194376

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

African (AFR) AF: 0.0690 AC: 735 AN: 10656

American (AMR) AF: 0.164 AC: 2525 AN: 15440

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 1415 AN: 12206

East Asian (EAS) AF: 0.293 AC: 7434 AN: 25370

South Asian (SAS) AF: 0.150 AC: 4297 AN: 28666

European-Finnish (FIN) AF: 0.139 AC: 3812 AN: 27444

Middle Eastern (MID) AF: 0.123 AC: 253 AN: 2056

European-Non Finnish (NFE) AF: 0.132 AC: 29621 AN: 223994

Other (OTH) AF: 0.140 AC: 2987 AN: 21284

⚠️ 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 AF: 0.163 AC: 22052 AN: 135336 Hom.: 1990 Cov.: 0 AF XY: 0.166 AC XY: 10833 AN XY: 65102

African (AFR) AF: 0.0708 AC: 2637 AN: 37262

American (AMR) AF: 0.196 AC: 2669 AN: 13624

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 506 AN: 3192

East Asian (EAS) AF: 0.337 AC: 1650 AN: 4890

South Asian (SAS) AF: 0.232 AC: 995 AN: 4286

European-Finnish (FIN) AF: 0.192 AC: 1357 AN: 7082

Middle Eastern (MID) AF: 0.143 AC: 38 AN: 266

European-Non Finnish (NFE) AF: 0.190 AC: 11798 AN: 62044

Other (OTH) AF: 0.169 AC: 315 AN: 1860

Alfa AF: 0.00 Hom.: 21

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs200558502; hg19: chr7-93063701; COSMIC: COSV64006381;