NM_001742.4:c.1149+125A>T

Variant names:

• chr7-93435827-T-A
• rs34229119
• NM_001742.4:c.1149+125A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001742.4(CALCR):​c.1149+125A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 137,558 control chromosomes in the GnomAD database, including 26,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (26751 hom., cov: 22)
  • Exomes 𝑓: 0.52 (14142 hom.)
  • Failed GnomAD Quality Control
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.781
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 7-93435827-T-A is Benign according to our data. Variant chr7-93435827-T-A is described in ClinVar as Benign. ClinVar VariationId is 1228199.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 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+125A>T		intron	N/A	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.1197+125A>T		intron	N/A	NP_001158209.2	A0A0A0MSQ7
	CALCR	NM_001164738.2		c.1149+125A>T		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+125A>T		intron	N/A	ENSP00000389295.1	P30988-2
	CALCR	ENST00000394441.5	TSL:1	c.1149+125A>T		intron	N/A	ENSP00000377959.1	P30988-2
	CALCR	ENST00000415529.2	TSL:1	n.*374+125A>T		intron	N/A	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes AF: 0.625 AC: 85965 AN: 137506 Hom.: 26760 Cov.: 22

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.670

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.516 AC: 51201 AN: 99232 Hom.: 14142 AF XY: 0.521 AC XY: 28478 AN XY: 54618

African (AFR) AF: 0.539 AC: 1254 AN: 2328

American (AMR) AF: 0.690 AC: 1925 AN: 2788

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1626 AN: 2930

East Asian (EAS) AF: 0.862 AC: 5866 AN: 6804

South Asian (SAS) AF: 0.555 AC: 618 AN: 1114

European-Finnish (FIN) AF: 0.343 AC: 4088 AN: 11920

Middle Eastern (MID) AF: 0.603 AC: 240 AN: 398

European-Non Finnish (NFE) AF: 0.497 AC: 32583 AN: 65566

Other (OTH) AF: 0.557 AC: 3001 AN: 5384

GnomAD4 genome AF: 0.625 AC: 85979 AN: 137558 Hom.: 26751 Cov.: 22 AF XY: 0.621 AC XY: 41205 AN XY: 66326

African (AFR) AF: 0.630 AC: 22339 AN: 35452

American (AMR) AF: 0.728 AC: 9914 AN: 13612

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2312 AN: 3336

East Asian (EAS) AF: 0.877 AC: 4234 AN: 4826

South Asian (SAS) AF: 0.643 AC: 2859 AN: 4444

European-Finnish (FIN) AF: 0.429 AC: 3448 AN: 8042

Middle Eastern (MID) AF: 0.705 AC: 186 AN: 264

European-Non Finnish (NFE) AF: 0.601 AC: 38970 AN: 64822

Other (OTH) AF: 0.670 AC: 1268 AN: 1892

Alfa AF: 0.435 Hom.: 211

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
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		-0.78
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: rs34229119; hg19: chr7-93065139; COSMIC: COSV64008217;