11-66314996-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020404.3(CD248):​c.2032G>A​(p.Glu678Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,611,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

CD248
NM_020404.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.104
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.039093435).
BS2
High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD248NM_020404.3 linkc.2032G>A p.Glu678Lys 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.2032G>A p.Glu678Lys missense_variant Exon 1 of 1 6 NM_020404.3 ENSP00000308117.3 Q9HCU0-1
ENSG00000254458ENST00000534065.1 linkn.140+2004C>T intron_variant Intron 1 of 1 4

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000101
AC:
25
AN:
247490
Hom.:
0
AF XY:
0.0000969
AC XY:
13
AN XY:
134182
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000955
Gnomad NFE exome
AF:
0.000179
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.000104
AC:
152
AN:
1458852
Hom.:
0
Cov.:
31
AF XY:
0.000113
AC XY:
82
AN XY:
725470
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000573
Gnomad4 NFE exome
AF:
0.000125
Gnomad4 OTH exome
AF:
0.0000996
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152314
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000849
Hom.:
0
Bravo
AF:
0.0000869
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2032G>A (p.E678K) alteration is located in exon 1 (coding exon 1) of the CD248 gene. This alteration results from a G to A substitution at nucleotide position 2032, causing the glutamic acid (E) at amino acid position 678 to be replaced by a lysine (K). 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
0.088
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.053
T
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.62
T
M_CAP
Uncertain
0.094
D
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.16
N
REVEL
Benign
0.21
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.074
T
Polyphen
0.0010
B
Vest4
0.17
MVP
0.24
MPC
0.39
ClinPred
0.073
T
GERP RS
2.6
Varity_R
0.081
gMVP
0.33

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: rs373617917; hg19: chr11-66082467; COSMIC: COSV60935923; API