12-108292096-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.169

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMKLR1	NM_001142343.2	c.867G>T	p.Met289Ile	missense_variant	4/4	ENST00000550402.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMKLR1	ENST00000550402.6	c.867G>T	p.Met289Ile	missense_variant	4/4	1	NM_001142343.2	A1
CMKLR1	ENST00000552995.5	c.861G>T	p.Met287Ile	missense_variant	3/3	1		P4
CMKLR1	ENST00000312143.11	c.867G>T	p.Met289Ile	missense_variant	3/3	2		A1
CMKLR1	ENST00000412676.5	c.867G>T	p.Met289Ile	missense_variant	3/3	3		A1

Frequencies

GnomAD3 genomes AF: 0.00793 AC: 1207 AN: 152178 Hom.: 19 Cov.: 33

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.: 7 AF XY: 0.00143 AC XY: 194 AN XY: 135224

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.: 12 Cov.: 30 AF XY: 0.000624 AC XY: 454 AN XY: 727236

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.: 19 Cov.: 33 AF XY: 0.00765 AC XY: 570 AN XY: 74476

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.: 2

Bravo AF: 0.00862

ESP6500AA AF: 0.0229 AC: 96

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.00244 AC: 296

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.59	T
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	N
LIST_S2	Benign	0.14	T;.;T;.
MetaRNN	Benign	0.0042	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.34	T
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	T
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

Other links and lift over

dbSNP: rs116531815; hg19: chr12-108685873;