7-93426496-C-A

Variant names:

• chr7-93426496-C-A
• rs150335791
• NM_001742.4:c.1285G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001742.4(CALCR):​c.1285G>T​(p.Ala429Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,613,770 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: CALCR NM_001742.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0250
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00876224).
• BP6: Variant 7-93426496-C-A is Benign according to our data. Variant chr7-93426496-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 731330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1285G>T	p.Ala429Ser	missense	Exon 14 of 14	NP_001733.1	P30988-2
	CALCR	NM_001164737.3		c.1333G>T	p.Ala445Ser	missense	Exon 16 of 16	NP_001158209.2	A0A0A0MSQ7
	CALCR	NM_001164738.2		c.1285G>T	p.Ala429Ser	missense	Exon 13 of 13	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.1285G>T	p.Ala429Ser	missense	Exon 14 of 14	ENSP00000389295.1	P30988-2
	CALCR	ENST00000394441.5	TSL:1	c.1285G>T	p.Ala429Ser	missense	Exon 13 of 13	ENSP00000377959.1	P30988-2
	CALCR	ENST00000415529.2	TSL:1	n.*510G>T		non_coding_transcript_exon	Exon 13 of 13	ENSP00000413179.1	P30988-5

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 301 AN: 152134 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00688

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000624 AC: 157 AN: 251402 AF XY: 0.000442

Gnomad AFR exome AF: 0.00843

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000200 AC: 293 AN: 1461518 Hom.: 1 Cov.: 31 AF XY: 0.000190 AC XY: 138 AN XY: 727108

African (AFR) AF: 0.00702 AC: 235 AN: 33468

American (AMR) AF: 0.000581 AC: 26 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111692

Other (OTH) AF: 0.000414 AC: 25 AN: 60382

GnomAD4 genome AF: 0.00198 AC: 302 AN: 152252 Hom.: 1 Cov.: 32 AF XY: 0.00199 AC XY: 148 AN XY: 74426

African (AFR) AF: 0.00688 AC: 286 AN: 41548

American (AMR) AF: 0.000914 AC: 14 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000682 Hom.: 3

Bravo AF: 0.00233

ESP6500AA AF: 0.00590 AC: 26

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000766 AC: 93

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.025
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.60	N
REVEL	Benign	0.099
Sift	Benign	0.68	T
Sift4G	Benign	0.53	T
Vest4		0.11
MVP		0.75
MPC		0.19
ClinPred		0.039	T
GERP RS		4.2
gMVP		0.39
Mutation Taster		=97/3	polymorphism

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: rs150335791; hg19: chr7-93055808;