rs374433270

Variant names:

• chr12-108292358-G-A
• rs374433270
• NM_001142343.2:c.605C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-108292358-G-A
• chr12-108292358-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001142343.2(CMKLR1):​c.605C>T​(p.Ser202Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CMKLR1 NM_001142343.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0120
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036455214).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142343.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMKLR1	NM_001142343.2	MANE Select	c.605C>T	p.Ser202Leu	missense	Exon 4 of 4	NP_001135815.1	Q99788-1
	CMKLR1	NM_001142344.2		c.605C>T	p.Ser202Leu	missense	Exon 3 of 3	NP_001135816.1	Q99788-1
	CMKLR1	NM_001142345.2		c.605C>T	p.Ser202Leu	missense	Exon 3 of 3	NP_001135817.1	Q99788-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMKLR1	ENST00000550402.6	TSL:1 MANE Select	c.605C>T	p.Ser202Leu	missense	Exon 4 of 4	ENSP00000449716.1	Q99788-1
	CMKLR1	ENST00000552995.5	TSL:1	c.599C>T	p.Ser200Leu	missense	Exon 3 of 3	ENSP00000447579.1	Q99788-2
	CMKLR1	ENST00000312143.11	TSL:2	c.605C>T	p.Ser202Leu	missense	Exon 3 of 3	ENSP00000311733.7	Q99788-1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000321 AC: 8 AN: 249372 AF XY: 0.0000296

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461866 Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74454

African (AFR) AF: 0.0000722 AC: 3 AN: 41566

American (AMR) AF: 0.000327 AC: 5 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.000239 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.47
DANN	Benign	0.72
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N
PhyloP100		-0.012
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.090
Sift	Benign	0.31	T
Sift4G	Benign	0.31	T
Polyphen		0.0020	B
Vest4		0.066
MVP		0.53
MPC		0.14
ClinPred		0.0053	T
GERP RS		1.6
Varity_R		0.022
gMVP		0.18
Mutation Taster		=97/3	polymorphism

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: rs374433270; hg19: chr12-108686135; COSMIC: COSV106094879; COSMIC: COSV106094879;