rs1706287

Variant names:

• chr2-187359330-A-G
• rs1706287
• NM_005795.6:c.782-58T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-187359330-A-G
• chr2-187359330-A-C
• chr2-187359330-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005795.6(CALCRL):​c.782-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,243,314 control chromosomes in the GnomAD database, including 463,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (57602 hom., cov: 31)
  • Exomes 𝑓: 0.86 (406044 hom.)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00500
• Publications: 6 publications found

Genes affected

CALCRL (HGNC:16709): (calcitonin receptor like receptor) Enables adrenomedullin binding activity; adrenomedullin receptor activity; and calcitonin gene-related peptide receptor activity. Involved in several processes, including G protein-coupled receptor signaling pathway; cellular response to sucrose stimulus; and receptor internalization. Located in endoplasmic reticulum; endosome; and lysosome. Part of CGRP receptor complex and adrenomedullin receptor complex. Colocalizes with plasma membrane. Implicated in hereditary lymphedema. [provided by Alliance of Genome Resources, Apr 2022]

CALCRL-AS1 (HGNC:55863): (CALCRL and TFPI antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-187359330-A-G is Benign according to our data. Variant chr2-187359330-A-G is described in ClinVar as Benign. ClinVar VariationId is 1192648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005795.6. 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
	CALCRL	NM_005795.6	MANE Select	c.782-58T>C		intron	N/A	NP_005786.1	Q16602
	CALCRL	NM_001271751.2		c.782-58T>C		intron	N/A	NP_001258680.1	Q16602
	CALCRL	NM_001369434.1		c.782-58T>C		intron	N/A	NP_001356363.1	Q16602

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCRL	ENST00000392370.8	TSL:1 MANE Select	c.782-58T>C		intron	N/A	ENSP00000376177.3	Q16602
	CALCRL	ENST00000409998.5	TSL:5	c.782-58T>C		intron	N/A	ENSP00000386972.1	Q16602
	CALCRL	ENST00000410068.5	TSL:2	c.782-58T>C		intron	N/A	ENSP00000387190.1	Q16602

Frequencies

GnomAD3 genomes AF: 0.869 AC: 131928 AN: 151798 Hom.: 57548 Cov.: 31

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.870

GnomAD4 exome AF: 0.862 AC: 940807 AN: 1091398 Hom.: 406044 AF XY: 0.860 AC XY: 467543 AN XY: 543446

African (AFR) AF: 0.915 AC: 21763 AN: 23792

American (AMR) AF: 0.804 AC: 16378 AN: 20360

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 18523 AN: 20426

East Asian (EAS) AF: 0.756 AC: 25334 AN: 33520

South Asian (SAS) AF: 0.822 AC: 50886 AN: 61908

European-Finnish (FIN) AF: 0.885 AC: 39626 AN: 44758

Middle Eastern (MID) AF: 0.898 AC: 2953 AN: 3288

European-Non Finnish (NFE) AF: 0.866 AC: 724647 AN: 836448

Other (OTH) AF: 0.868 AC: 40697 AN: 46898

GnomAD4 genome AF: 0.869 AC: 132037 AN: 151916 Hom.: 57602 Cov.: 31 AF XY: 0.867 AC XY: 64405 AN XY: 74260

African (AFR) AF: 0.909 AC: 37677 AN: 41456

American (AMR) AF: 0.818 AC: 12462 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3163 AN: 3468

East Asian (EAS) AF: 0.752 AC: 3876 AN: 5152

South Asian (SAS) AF: 0.801 AC: 3869 AN: 4828

European-Finnish (FIN) AF: 0.884 AC: 9309 AN: 10532

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58774 AN: 67932

Other (OTH) AF: 0.871 AC: 1838 AN: 2110

Alfa AF: 0.872 Hom.: 9664

Bravo AF: 0.867

Asia WGS AF: 0.794 AC: 2745 AN: 3462

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Lymphatic malformation 8 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		0.0050
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: rs1706287; hg19: chr2-188224057;