Genetic Variant CD248:p.His457Arg (chr11-66315658-T-C) – ACMG Classification: Benign (-12 pts)

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

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]

CD248 links:

ENSG00000254458 (HGNC:):

ENSG00000254458 links:

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
CD248	NM_020404.3 link	c.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	UniProt
CD248	ENST00000311330.4 link	c.1370A>G	p.His457Arg	missense_variant	Exon 1 of 1	6	NM_020404.3	ENSP00000308117.3	Q9HCU0-1
ENSG00000254458	ENST00000534065.1 link	n.140+2666T>C		intron_variant	Intron 1 of 1	4
ENSG00000254756	ENST00000820635.1 link	n.134+3495T>C		intron_variant	Intron 1 of 3
ENSG00000254756	ENST00000820636.1 link	n.96+3495T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57073

AN:

151514

Hom.:

11816

Cov.:

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.:

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

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

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.:

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:

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

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

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

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.1

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.025

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.18

MetaRNN

Benign

0.000039

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.68

PhyloP100

0.66

PrimateAI

Benign

0.31

PROVEAN

Benign

1.1

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.026

MPC

0.43

ClinPred

0.0027

GERP RS

1.6

Varity_R

0.021

gMVP

0.22

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over