11-66314924-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020404.3(CD248):​c.2104C>A​(p.Leu702Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L702V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CD248
NM_020404.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

Publications

0 publications found
Variant links:
Genes affected
CD248 (HGNC:18219): (CD248 molecule) Predicted to enable extracellular matrix binding activity and extracellular matrix protein binding activity. Predicted to be involved in cell migration. Predicted to act upstream of or within several processes, including anatomical structure regression; lymph node development; and positive regulation of endothelial cell apoptotic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19825584).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD248NM_020404.3 linkc.2104C>A p.Leu702Met missense_variant Exon 1 of 1 ENST00000311330.4 NP_065137.1 Q9HCU0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD248ENST00000311330.4 linkc.2104C>A p.Leu702Met missense_variant Exon 1 of 1 6 NM_020404.3 ENSP00000308117.3 Q9HCU0-1
ENSG00000254458ENST00000534065.1 linkn.140+1932G>T intron_variant Intron 1 of 1 4
ENSG00000254756ENST00000820635.1 linkn.134+2761G>T intron_variant Intron 1 of 3
ENSG00000254756ENST00000820636.1 linkn.96+2761G>T intron_variant Intron 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461040
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726798
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44668
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26110
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39684
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86204
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52900
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111876
Other (OTH)
AF:
0.00
AC:
0
AN:
60352
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.027
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.031
T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.22
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.053
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.34
T
MutationAssessor
Benign
1.1
L
PhyloP100
1.8
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.15
N
REVEL
Benign
0.20
Sift
Benign
0.36
T
Sift4G
Benign
0.71
T
Polyphen
0.38
B
Vest4
0.28
MutPred
0.37
Loss of helix (P = 0.2271);
MVP
0.39
MPC
1.1
ClinPred
0.35
T
GERP RS
3.2
Varity_R
0.075
gMVP
0.34
Mutation Taster
=88/12
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

Publications

Other links and lift over

dbSNP: rs2134915749; hg19: chr11-66082395; API