12-108305255-C-T

Position:

• chr12-108305255-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMKLR1	NM_001142343.2	c.-73-11591G>A		intron_variant		ENST00000550402.6	NP_001135815.1
CMKLR1	NM_001142344.2	c.-73-11591G>A		intron_variant			NP_001135816.1
CMKLR1	NM_001142345.2	c.-73-11591G>A		intron_variant			NP_001135817.1
CMKLR1	NM_004072.3	c.-3-12296G>A		intron_variant			NP_004063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMKLR1	ENST00000550402.6	c.-73-11591G>A		intron_variant		1	NM_001142343.2	ENSP00000449716	A1

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

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.653

Alfa AF: 0.656 Hom.: 72050

Bravo AF: 0.703

Asia WGS AF: 0.619 AC: 2150 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.45

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: rs1878022; hg19: chr12-108699032; COSMIC: COSV56435971;