chr11-66315658-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020404.3(CD248):​c.1370A>G​(p.His457Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,613,238 control chromosomes in the GnomAD database, including 153,883 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 11818 hom., cov: 31)
Exomes 𝑓: 0.43 ( 142065 hom. )

Consequence

CD248
NM_020404.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.663

Publications

37 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=3.8679565E-5).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD248NM_020404.3 linkc.1370A>G p.His457Arg 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.1370A>G p.His457Arg missense_variant Exon 1 of 1 6 NM_020404.3 ENSP00000308117.3 Q9HCU0-1
ENSG00000254458ENST00000534065.1 linkn.140+2666T>C intron_variant Intron 1 of 1 4
ENSG00000254756ENST00000820635.1 linkn.134+3495T>C intron_variant Intron 1 of 3
ENSG00000254756ENST00000820636.1 linkn.96+3495T>C intron_variant Intron 1 of 2

Frequencies

GnomAD3 genomes
AF:
0.377
AC:
57073
AN:
151514
Hom.:
11816
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.224
Gnomad AMI
AF:
0.567
Gnomad AMR
AF:
0.444
Gnomad ASJ
AF:
0.443
Gnomad EAS
AF:
0.193
Gnomad SAS
AF:
0.233
Gnomad FIN
AF:
0.519
Gnomad MID
AF:
0.309
Gnomad NFE
AF:
0.451
Gnomad OTH
AF:
0.362
GnomAD2 exomes
AF:
0.409
AC:
102635
AN:
250962
AF XY:
0.402
show subpopulations
Gnomad AFR exome
AF:
0.217
Gnomad AMR exome
AF:
0.564
Gnomad ASJ exome
AF:
0.450
Gnomad EAS exome
AF:
0.183
Gnomad FIN exome
AF:
0.512
Gnomad NFE exome
AF:
0.448
Gnomad OTH exome
AF:
0.424
GnomAD4 exome
AF:
0.433
AC:
633065
AN:
1461606
Hom.:
142065
Cov.:
69
AF XY:
0.427
AC XY:
310342
AN XY:
727084
show subpopulations
African (AFR)
AF:
0.204
AC:
6820
AN:
33480
American (AMR)
AF:
0.554
AC:
24765
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.453
AC:
11847
AN:
26126
East Asian (EAS)
AF:
0.205
AC:
8130
AN:
39700
South Asian (SAS)
AF:
0.243
AC:
20991
AN:
86254
European-Finnish (FIN)
AF:
0.511
AC:
27224
AN:
53270
Middle Eastern (MID)
AF:
0.346
AC:
1998
AN:
5768
European-Non Finnish (NFE)
AF:
0.456
AC:
506566
AN:
1111912
Other (OTH)
AF:
0.409
AC:
24724
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
23194
46389
69583
92778
115972
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
15092
30184
45276
60368
75460
<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
AF:
0.377
AC:
57093
AN:
151632
Hom.:
11818
Cov.:
31
AF XY:
0.376
AC XY:
27847
AN XY:
74040
show subpopulations
African (AFR)
AF:
0.224
AC:
9254
AN:
41278
American (AMR)
AF:
0.445
AC:
6785
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
0.443
AC:
1533
AN:
3462
East Asian (EAS)
AF:
0.193
AC:
989
AN:
5124
South Asian (SAS)
AF:
0.233
AC:
1118
AN:
4808
European-Finnish (FIN)
AF:
0.519
AC:
5465
AN:
10534
Middle Eastern (MID)
AF:
0.312
AC:
91
AN:
292
European-Non Finnish (NFE)
AF:
0.451
AC:
30590
AN:
67864
Other (OTH)
AF:
0.357
AC:
752
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1714
3429
5143
6858
8572
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
536
1072
1608
2144
2680
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.422
Hom.:
64624
Bravo
AF:
0.372
TwinsUK
AF:
0.462
AC:
1713
ALSPAC
AF:
0.456
AC:
1758
ESP6500AA
AF:
0.227
AC:
999
ESP6500EA
AF:
0.452
AC:
3885
ExAC
AF:
0.399
AC:
48456
Asia WGS
AF:
0.241
AC:
840
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
2.1
DANN
Benign
0.50
DEOGEN2
Benign
0.025
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0059
N
LIST_S2
Benign
0.18
T
MetaRNN
Benign
0.000039
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.68
N
PhyloP100
0.66
PrimateAI
Benign
0.31
T
PROVEAN
Benign
1.1
N
REVEL
Benign
0.19
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.026
MPC
0.43
ClinPred
0.0027
T
GERP RS
1.6
Varity_R
0.021
gMVP
0.22
Mutation Taster
=99/1
polymorphism (auto)

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: rs3741367; hg19: chr11-66083129; COSMIC: COSV60935755; API