7-93435827-T-A

Position:

• chr7-93435827-T-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.1149+125A>T		intron_variant		ENST00000426151.7
CALCR	NM_001164737.3	c.1197+125A>T		intron_variant
CALCR	NM_001164738.2	c.1149+125A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.1149+125A>T		intron_variant		1	NM_001742.4	P1

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

Gnomad4 AFR exome AF: 0.539

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.862

Gnomad4 SAS exome AF: 0.555

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.557

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

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.670

Alfa AF: 0.435 Hom.: 211

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.41

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

LitVar

Other links and lift over

dbSNP: rs34229119; hg19: chr7-93065139; COSMIC: COSV64008217;