Genetic Variant NM_005795.6:c.*697C>T (chr2-187345487-G-A) – 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.*697C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,894 control chromosomes in the GnomAD database, including 28,477 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 0.60 ( 28381 hom., cov: 31)

Exomes 𝑓: 0.69 ( 96 hom. )

Consequence

CALCRL
NM_005795.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.829

Publications

9 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALCRL	NM_005795.6	MANE Select	c.*697C>T	3_prime_UTR	Exon 15 of 15	NP_005786.1	Q16602
CALCRL	NM_001271751.2		c.*697C>T	3_prime_UTR	Exon 14 of 14	NP_001258680.1	Q16602
CALCRL	NM_001369434.1		c.*697C>T	3_prime_UTR	Exon 16 of 16	NP_001356363.1	Q16602

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALCRL	ENST00000392370.8	TSL:1 MANE Select	c.*697C>T	3_prime_UTR	Exon 15 of 15	ENSP00000376177.3	Q16602
CALCRL	ENST00000409998.5	TSL:5	c.*697C>T	3_prime_UTR	Exon 16 of 16	ENSP00000386972.1	Q16602
CALCRL	ENST00000897822.1		c.*697C>T	3_prime_UTR	Exon 14 of 14	ENSP00000567881.1

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90576

AN:

151356

Hom.:

28368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.600

Gnomad AMR

AF:

0.690

Gnomad ASJ

AF:

0.587

Gnomad EAS

AF:

0.864

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.691

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.576

GnomAD4 exome

AF:

0.688

AC:

289

AN:

420

Hom.:

Cov.:

AF XY:

0.720

AC XY:

180

AN XY:

250

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.686

AC:

284

AN:

414

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.598

AC:

90631

AN:

151474

Hom.:

28381

Cov.:

AF XY:

0.604

AC XY:

44689

AN XY:

74016

show subpopulations

African (AFR)

AF:

0.409

AC:

16919

AN:

41332

American (AMR)

AF:

0.690

AC:

10447

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

2030

AN:

3458

East Asian (EAS)

AF:

0.864

AC:

4460

AN:

5160

South Asian (SAS)

AF:

0.639

AC:

3081

AN:

4818

European-Finnish (FIN)

AF:

0.691

AC:

7309

AN:

10578

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.657

AC:

44485

AN:

67700

Other (OTH)

AF:

0.571

AC:

1198

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1719

3437

5156

6874

8593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.631

Hom.:

31235

Bravo

AF:

0.592

Asia WGS

AF:

0.701

AC:

2440

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.41

(source)

DANN

Benign

0.66

PhyloP100

-0.83

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over