NM_001742.4:c.1149+124_1149+127delTATT

Variant names:

• chr7-93435824-TAATA-T
• rs140043489
• NM_001742.4:c.1149+124_1149+127delTATT

Variant summary

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

The NM_001742.4(CALCR):​c.1149+124_1149+127delTATT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 310,956 control chromosomes in the GnomAD database, including 458 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (219 hom., cov: 22)
  • Exomes 𝑓: 0.025 (239 hom.)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170
• 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 7-93435824-TAATA-T is Benign according to our data. Variant chr7-93435824-TAATA-T is described in ClinVar as Benign. ClinVar VariationId is 1263502.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0948 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.1149+124_1149+127delTATT		intron	N/A	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.1197+124_1197+127delTATT		intron	N/A	NP_001158209.2	A0A0A0MSQ7
	CALCR	NM_001164738.2		c.1149+124_1149+127delTATT		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.1149+124_1149+127delTATT		intron	N/A	ENSP00000389295.1	P30988-2
	CALCR	ENST00000394441.5	TSL:1	c.1149+124_1149+127delTATT		intron	N/A	ENSP00000377959.1	P30988-2
	CALCR	ENST00000415529.2	TSL:1	n.*374+124_*374+127delTATT		intron	N/A	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4539 AN: 145076 Hom.: 220 Cov.: 22

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.00695

Gnomad EAS AF: 0.00122

Gnomad SAS AF: 0.00425

Gnomad FIN AF: 0.00601

Gnomad MID AF: 0.0296

Gnomad NFE AF: 0.00350

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.0253 AC: 4196 AN: 165800 Hom.: 239 AF XY: 0.0237 AC XY: 2106 AN XY: 88840

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

African (AFR) AF: 0.0849 AC: 359 AN: 4230

American (AMR) AF: 0.0289 AC: 139 AN: 4814

Ashkenazi Jewish (ASJ) AF: 0.0206 AC: 107 AN: 5182

East Asian (EAS) AF: 0.00484 AC: 64 AN: 13228

South Asian (SAS) AF: 0.0408 AC: 84 AN: 2060

European-Finnish (FIN) AF: 0.0710 AC: 1284 AN: 18082

Middle Eastern (MID) AF: 0.0324 AC: 24 AN: 740

European-Non Finnish (NFE) AF: 0.0176 AC: 1899 AN: 107878

Other (OTH) AF: 0.0246 AC: 236 AN: 9586

⚠️ 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: 0.0313 AC: 4545 AN: 145156 Hom.: 219 Cov.: 22 AF XY: 0.0312 AC XY: 2210 AN XY: 70796

African (AFR) AF: 0.0974 AC: 3862 AN: 39656

American (AMR) AF: 0.0195 AC: 286 AN: 14686

Ashkenazi Jewish (ASJ) AF: 0.00695 AC: 23 AN: 3308

East Asian (EAS) AF: 0.00122 AC: 6 AN: 4910

South Asian (SAS) AF: 0.00426 AC: 20 AN: 4692

European-Finnish (FIN) AF: 0.00601 AC: 56 AN: 9312

Middle Eastern (MID) AF: 0.0324 AC: 9 AN: 278

European-Non Finnish (NFE) AF: 0.00350 AC: 229 AN: 65420

Other (OTH) AF: 0.0265 AC: 54 AN: 2036

Alfa AF: 0.0180 Hom.: 14

ClinVar

ClinVar submissions

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		-0.017
Mutation Taster		=100/0	polymorphism (auto)

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: rs140043489; hg19: chr7-93065136;