12-108305255-C-T

Variant names:

• chr12-108305255-C-T
• rs1878022
• NM_001142343.2:c.-73-11591G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142343.2(CMKLR1):​c.-73-11591G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,144 control chromosomes in the GnomAD database, including 37,776 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 0.70 (37776 hom., cov: 32)
• Consequence: CMKLR1 NM_001142343.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 30 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

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.-73-11591G>A		intron	N/A	NP_001135815.1	Q99788-1
	CMKLR1	NM_001142344.2		c.-73-11591G>A		intron	N/A	NP_001135816.1	Q99788-1
	CMKLR1	NM_001142345.2		c.-73-11591G>A		intron	N/A	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.-73-11591G>A		intron	N/A	ENSP00000449716.1	Q99788-1
	CMKLR1	ENST00000552995.5	TSL:1	c.-3-12296G>A		intron	N/A	ENSP00000447579.1	Q99788-2
	CMKLR1	ENST00000312143.11	TSL:2	c.-73-11591G>A		intron	N/A	ENSP00000311733.7	Q99788-1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106181 AN: 152026 Hom.: 37734 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.699 AC: 106289 AN: 152144 Hom.: 37776 Cov.: 32 AF XY: 0.695 AC XY: 51707 AN XY: 74366

African (AFR) AF: 0.835 AC: 34696 AN: 41530

American (AMR) AF: 0.614 AC: 9389 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3470

East Asian (EAS) AF: 0.567 AC: 2919 AN: 5152

South Asian (SAS) AF: 0.668 AC: 3215 AN: 4814

European-Finnish (FIN) AF: 0.664 AC: 7033 AN: 10588

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44638 AN: 67982

Other (OTH) AF: 0.653 AC: 1382 AN: 2116

Alfa AF: 0.659 Hom.: 96810

Bravo AF: 0.703

Asia WGS AF: 0.619 AC: 2150 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.45
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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: rs1878022; hg19: chr12-108699032;