rs3771084

Variant names:

• chr2-187378906-A-G
• rs3771084
• NM_005795.6:c.500+34T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-187378906-A-G
• chr2-187378906-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005795.6(CALCRL):​c.500+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,253,112 control chromosomes in the GnomAD database, including 209,728 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (22345 hom., cov: 32)
  • Exomes 𝑓: 0.58 (187383 hom.)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCRL	NM_005795.6	MANE Select	c.500+34T>C		intron	N/A	NP_005786.1
	CALCRL	NM_001271751.2		c.500+34T>C		intron	N/A	NP_001258680.1
	CALCRL	NM_001369434.1		c.500+34T>C		intron	N/A	NP_001356363.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCRL	ENST00000392370.8	TSL:1 MANE Select	c.500+34T>C		intron	N/A	ENSP00000376177.3
	CALCRL	ENST00000409998.5	TSL:5	c.500+34T>C		intron	N/A	ENSP00000386972.1
	CALCRL	ENST00000410068.5	TSL:2	c.500+34T>C		intron	N/A	ENSP00000387190.1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81056 AN: 151796 Hom.: 22334 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.521

GnomAD2 exomes AF: 0.588 AC: 140870 AN: 239580 AF XY: 0.577

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.747

Gnomad ASJ exome AF: 0.573

Gnomad EAS exome AF: 0.794

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.557

Gnomad OTH exome AF: 0.574

GnomAD4 exome AF: 0.578 AC: 636625 AN: 1101198 Hom.: 187383 Cov.: 14 AF XY: 0.572 AC XY: 322723 AN XY: 563896

African (AFR) AF: 0.406 AC: 10518 AN: 25898

American (AMR) AF: 0.732 AC: 31711 AN: 43350

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 13470 AN: 23378

East Asian (EAS) AF: 0.816 AC: 30832 AN: 37806

South Asian (SAS) AF: 0.477 AC: 36314 AN: 76054

European-Finnish (FIN) AF: 0.615 AC: 30610 AN: 49784

Middle Eastern (MID) AF: 0.480 AC: 1831 AN: 3812

European-Non Finnish (NFE) AF: 0.573 AC: 453999 AN: 792848

Other (OTH) AF: 0.566 AC: 27340 AN: 48268

GnomAD4 genome AF: 0.534 AC: 81093 AN: 151914 Hom.: 22345 Cov.: 32 AF XY: 0.539 AC XY: 40036 AN XY: 74224

African (AFR) AF: 0.406 AC: 16838 AN: 41436

American (AMR) AF: 0.642 AC: 9796 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1994 AN: 3466

East Asian (EAS) AF: 0.780 AC: 4037 AN: 5178

South Asian (SAS) AF: 0.482 AC: 2330 AN: 4830

European-Finnish (FIN) AF: 0.623 AC: 6570 AN: 10552

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37816 AN: 67878

Other (OTH) AF: 0.517 AC: 1092 AN: 2114

Alfa AF: 0.546 Hom.: 64105

Bravo AF: 0.537

Asia WGS AF: 0.594 AC: 2057 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.40
PhyloP100		-0.11
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: rs3771084; hg19: chr2-188243633;