12-108292096-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001142343.2(CMKLR1):c.867G>T(p.Met289Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,614,172 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 19 hom., cov: 33)

Exomes 𝑓: 0.00074 ( 12 hom. )

Consequence

CMKLR1
NM_001142343.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.169

Variant links:

Genes affected

CMKLR1 (HGNC:2121): (chemerin chemokine-like receptor 1) Enables adipokinetic hormone binding activity and adipokinetic hormone receptor activity. Involved in several processes, including negative regulation of NF-kappaB transcription factor activity; positive regulation of macrophage chemotaxis; and regulation of calcium-mediated signaling. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CMKLR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042166114).

BP6

Variant 12-108292096-C-A is Benign according to our data. Variant chr12-108292096-C-A is described in ClinVar as [Benign]. Clinvar id is 708327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00793 (1207/152296) while in subpopulation AFR AF= 0.0285 (1184/41562). AF 95% confidence interval is 0.0271. There are 19 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMKLR1	NM_001142343.2 link	c.867G>T	p.Met289Ile	missense_variant	Exon 4 of 4	ENST00000550402.6	NP_001135815.1	Q99788-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CMKLR1	ENST00000550402.6 link	c.867G>T	p.Met289Ile	missense_variant	Exon 4 of 4	1	NM_001142343.2	ENSP00000449716.1	Q99788-1
CMKLR1	ENST00000552995.5 link	c.861G>T	p.Met287Ile	missense_variant	Exon 3 of 3	1		ENSP00000447579.1	Q99788-2
CMKLR1	ENST00000312143.11 link	c.867G>T	p.Met289Ile	missense_variant	Exon 3 of 3	2		ENSP00000311733.7	Q99788-1
CMKLR1	ENST00000412676.5 link	c.867G>T	p.Met289Ile	missense_variant	Exon 3 of 3	3		ENSP00000401293.1	Q99788-1

Frequencies

GnomAD3 genomes

AF:

0.00793

AC:

1207

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00193

AC:

480

AN:

249256

Hom.:

AF XY:

0.00143

AC XY:

194

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.000840

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000991

GnomAD4 exome

AF:

0.000742

AC:

1085

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000624

AC XY:

454

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0284

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00793

AC:

1207

AN:

152296

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

570

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0285

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00862

ESP6500AA

AF:

0.0229

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.00244

AC:

296

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.79

DANN

Benign

0.51

DEOGEN2

Benign

0.030

T;T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.14

T;.;T;.

MetaRNN

Benign

0.0042

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N;.;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.24

N;N;N;N

REVEL

Benign

0.070

Sift

Benign

0.58

T;T;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.12

MutPred

0.49

Gain of catalytic residue at L284 (P = 0.001);Gain of catalytic residue at L284 (P = 0.001);.;Gain of catalytic residue at L284 (P = 0.001);

MVP

0.50

MPC

0.17

ClinPred

0.00044

GERP RS

1.2

Varity_R

0.028

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over