16-66565987-G-A

Variant names:

• chr16-66565987-G-A
• rs2232729
• NM_016951.4:c.435G>A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_016951.4(CKLF):​c.435G>A​(p.Val145Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 1,612,022 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (57 hom.)
• Consequence: CKLF NM_016951.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.335

Genes affected

CKLF (HGNC:13253): (chemokine like factor) The product of this gene is a cytokine. Cytokines are small proteins that have an essential role in the immune and inflammatory responses. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 16. The protein encoded by this gene is a potent chemoattractant for neutrophils, monocytes and lymphocytes. It also can stimulate the proliferation of skeletal muscle cells. This protein may play important roles in inflammation and in the regeneration of skeletal muscle. Alternatively spliced transcript variants encoding different isoforms have been identified. Naturally occurring read-through transcription occurs between this locus and the neighboring locus CMTM1 (CKLF-like MARVEL transmembrane domain containing 1).[provided by RefSeq, Feb 2011]

CKLF-CMTM1 (HGNC:39977): (CKLF-CMTM1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring CKLF (chemokine-like factor) and CMTM1 (CKLF-like MARVEL transmembrane domain containing 1) genes on chromosome 16. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

ENSG00000277978 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-66565987-G-A is Benign according to our data. Variant chr16-66565987-G-A is described in ClinVar as [Benign]. Clinvar id is 782141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.335 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKLF	NM_016951.4	c.435G>A	p.Val145Val	synonymous_variant	Exon 4 of 4	ENST00000264001.9	NP_058647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKLF	ENST00000264001.9	c.435G>A	p.Val145Val	synonymous_variant	Exon 4 of 4	1	NM_016951.4	ENSP00000264001.5
CKLF-CMTM1	ENST00000616804.5	c.237+7639G>A		intron_variant	Intron 2 of 3	2		ENSP00000479319.1

Frequencies

GnomAD3 genomes AF: 0.00660 AC: 1003 AN: 152062 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00172

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00950

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00679 AC: 1706 AN: 251298 Hom.: 9 AF XY: 0.00653 AC XY: 887 AN XY: 135842

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00108

Gnomad FIN exome AF: 0.0180

Gnomad NFE exome AF: 0.00981

Gnomad OTH exome AF: 0.00799

GnomAD4 exome AF: 0.00764 AC: 11152 AN: 1459842 Hom.: 57 Cov.: 31 AF XY: 0.00739 AC XY: 5369 AN XY: 726368

Gnomad4 AFR exome AF: 0.00123

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.000421

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00124

Gnomad4 FIN exome AF: 0.0196

Gnomad4 NFE exome AF: 0.00852

Gnomad4 OTH exome AF: 0.00597

GnomAD4 genome AF: 0.00658 AC: 1002 AN: 152180 Hom.: 4 Cov.: 32 AF XY: 0.00694 AC XY: 516 AN XY: 74398

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.00949

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00754 Hom.: 4

Bravo AF: 0.00501

EpiCase AF: 0.00812

EpiControl AF: 0.00753

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2232729; hg19: chr16-66599890;