7-93435814-T-A

Position:

• chr7-93435814-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+138A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 229,306 control chromosomes in the GnomAD database, including 6,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (5447 hom., cov: 25)
  • Exomes 𝑓: 0.17 (1487 hom.)
• Consequence: CALCR NM_001742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.516

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=-0.9).
• BP6: Variant 7-93435814-T-A is Benign according to our data. Variant chr7-93435814-T-A is described in ClinVar as [Benign]. Clinvar id is 1182593.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCR	NM_001742.4	c.1149+138A>T		intron_variant		ENST00000426151.7
CALCR	NM_001164737.3	c.1197+138A>T		intron_variant
CALCR	NM_001164738.2	c.1149+138A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCR	ENST00000426151.7	c.1149+138A>T		intron_variant		1	NM_001742.4	P1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 37516 AN: 118512 Hom.: 5450 Cov.: 25

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.168 AC: 18634 AN: 110734 Hom.: 1487 AF XY: 0.175 AC XY: 10567 AN XY: 60394

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.0425

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0955

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.316 AC: 37519 AN: 118572 Hom.: 5447 Cov.: 25 AF XY: 0.308 AC XY: 17500 AN XY: 56750

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.348

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	-0.90
CADD	Benign	4.0
DANN	Benign	0.60

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: rs13234552; hg19: chr7-93065126; COSMIC: COSV64008213;