7-93434389-GAAAAA-GAAAAAAAAA

Variant names:

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

Variant summary

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

The NM_001742.4(CALCR):​c.1150-99_1150-96dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 507,760 control chromosomes in the GnomAD database, including 301 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (278 hom., cov: 0)
  • Exomes 𝑓: 0.023 (23 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-GAAAA is Benign according to our data. Variant chr7-93434389-G-GAAAA is described in ClinVar as Benign. ClinVar VariationId is 1270922.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 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.1150-99_1150-96dupTTTT		intron	N/A	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.1198-99_1198-96dupTTTT		intron	N/A	NP_001158209.2	A0A0A0MSQ7
	CALCR	NM_001164738.2		c.1150-99_1150-96dupTTTT		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_1150-95insTTTT		intron	N/A	ENSP00000389295.1	P30988-2
	CALCR	ENST00000394441.5	TSL:1	c.1150-96_1150-95insTTTT		intron	N/A	ENSP00000377959.1	P30988-2
	CALCR	ENST00000415529.2	TSL:1	n.*375-96_*375-95insTTTT		intron	N/A	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 7322 AN: 135332 Hom.: 278 Cov.: 0

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.0494

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.0463

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0731

Gnomad MID AF: 0.0490

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0509

GnomAD4 exome AF: 0.0227 AC: 8463 AN: 372386 Hom.: 23 AF XY: 0.0214 AC XY: 4226 AN XY: 197186

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

African (AFR) AF: 0.0271 AC: 292 AN: 10770

American (AMR) AF: 0.0790 AC: 1216 AN: 15390

Ashkenazi Jewish (ASJ) AF: 0.00875 AC: 109 AN: 12456

East Asian (EAS) AF: 0.0332 AC: 859 AN: 25866

South Asian (SAS) AF: 0.00887 AC: 260 AN: 29324

European-Finnish (FIN) AF: 0.0392 AC: 1083 AN: 27610

Middle Eastern (MID) AF: 0.0130 AC: 27 AN: 2072

European-Non Finnish (NFE) AF: 0.0180 AC: 4093 AN: 227316

Other (OTH) AF: 0.0243 AC: 524 AN: 21582

⚠️ 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: 0.0541 AC: 7327 AN: 135374 Hom.: 278 Cov.: 0 AF XY: 0.0561 AC XY: 3654 AN XY: 65124

African (AFR) AF: 0.0530 AC: 1971 AN: 37214

American (AMR) AF: 0.133 AC: 1806 AN: 13568

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 50 AN: 3204

East Asian (EAS) AF: 0.0467 AC: 229 AN: 4904

South Asian (SAS) AF: 0.0293 AC: 126 AN: 4296

European-Finnish (FIN) AF: 0.0731 AC: 518 AN: 7090

Middle Eastern (MID) AF: 0.0489 AC: 13 AN: 266

European-Non Finnish (NFE) AF: 0.0399 AC: 2479 AN: 62138

Other (OTH) AF: 0.0504 AC: 94 AN: 1864

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

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;