dbSNP rs3771084: CALCRL:c.500+34T>C (chr2-187378906-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.106

Publications

12 publications found

Variant links:

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 links:

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

CALCRL-AS1 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6 link	c.500+34T>C		intron_variant	Intron 8 of 14	ENST00000392370.8	NP_005786.1	Q16602

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8 link	c.500+34T>C		intron_variant	Intron 8 of 14	1	NM_005795.6	ENSP00000376177.3		Q16602

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

81056

AN:

151796

Hom.:

22334

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.572

AC XY:

322723

AN XY:

563896

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

12782

25565

38347

51130

63912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.534

AC:

81093

AN:

151914

Hom.:

22345

Cov.:

AF XY:

0.539

AC XY:

40036

AN XY:

74224

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1939

3878

5818

7757

9696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.18

(source)

DANN

Benign

0.40

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs3771084

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over