3-132601238-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016557.4(ACKR4):ā€‹c.841A>Gā€‹(p.Met281Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,613,736 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M281T) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.00011 ( 0 hom., cov: 29)
Exomes š‘“: 0.00023 ( 0 hom. )

Consequence

ACKR4
NM_016557.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60
Variant links:
Genes affected
ACKR4 (HGNC:1611): (atypical chemokine receptor 4) The protein encoded by this gene is a member of the G protein-coupled receptor family, and is a receptor for C-C type chemokines. This receptor has been shown to bind dendritic cell- and T cell-activated chemokines including CCL19/ELC, CCL21/SLC, and CCL25/TECK. A pseudogene of this gene is found on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2013]
ACAD11 (HGNC:30211): (acyl-CoA dehydrogenase family member 11) This gene encodes an acyl-CoA dehydrogenase enzyme with a preference for carbon chain lengths between 20 and 26. Naturally occurring read-through transcription occurs between the upstream gene NPHP3 (nephronophthisis 3 (adolescent)) and this gene. [provided by RefSeq, Aug 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15088382).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACKR4NM_016557.4 linkuse as main transcriptc.841A>G p.Met281Val missense_variant 2/2 ENST00000249887.3
ACAD11NM_032169.5 linkuse as main transcriptc.1621+1991T>C intron_variant ENST00000264990.11
NPHP3-ACAD11NR_037804.1 linkuse as main transcriptn.5623+1991T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACKR4ENST00000249887.3 linkuse as main transcriptc.841A>G p.Met281Val missense_variant 2/21 NM_016557.4 P1
ACAD11ENST00000264990.11 linkuse as main transcriptc.1621+1991T>C intron_variant 1 NM_032169.5 P1Q709F0-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152180
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000162
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.000227
AC:
332
AN:
1461556
Hom.:
0
Cov.:
32
AF XY:
0.000230
AC XY:
167
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000289
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152180
Hom.:
0
Cov.:
29
AF XY:
0.0000942
AC XY:
7
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000144
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 17, 2021The c.841A>G (p.M281V) alteration is located in exon 1 (coding exon 1) of the ACKR4 gene. This alteration results from a A to G substitution at nucleotide position 841, causing the methionine (M) at amino acid position 281 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
14
DANN
Benign
0.87
DEOGEN2
Benign
0.052
T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.43
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.62
T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.67
N
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.49
N
REVEL
Benign
0.035
Sift
Benign
0.19
T
Sift4G
Benign
0.11
T
Polyphen
0.0010
B
Vest4
0.38
MVP
0.34
ClinPred
0.026
T
GERP RS
1.6
Varity_R
0.094
gMVP
0.35

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368529492; hg19: chr3-132320082; API