chr7-93426496-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001742.4(CALCR):​c.1285G>A​(p.Ala429Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CALCR NM_001742.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06961653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCR	NM_001742.4	c.1285G>A	p.Ala429Thr	missense_variant	Exon 14 of 14	ENST00000426151.7	NP_001733.1
CALCR	NM_001164737.3	c.1333G>A	p.Ala445Thr	missense_variant	Exon 16 of 16		NP_001158209.2
CALCR	NM_001164738.2	c.1285G>A	p.Ala429Thr	missense_variant	Exon 13 of 13		NP_001158210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCR	ENST00000426151.7	c.1285G>A	p.Ala429Thr	missense_variant	Exon 14 of 14	1	NM_001742.4	ENSP00000389295.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461518 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.9
DANN	Benign	0.21
DEOGEN2	Benign	0.0071	.;T;T;T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.61	T;.;.;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.070	T;T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.9	N;N;N;.;N
REVEL	Benign	0.12
Sift	Benign	0.81	T;T;T;.;T
Sift4G	Benign	1.0	T;T;T;.;T
Vest4		0.072
MutPred		0.27		.;.;Gain of glycosylation at A429 (P = 0.0172);.;Gain of glycosylation at A429 (P = 0.0172);
MVP		0.61
MPC		0.19
ClinPred		0.18	T
GERP RS		4.2
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-93055808;