Genetic Variant CD248:p.Thr587Pro (chr11-66315269-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020404.3(CD248):c.1759A>C(p.Thr587Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,536,038 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

CD248
NM_020404.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.230

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]

CD248 links:

ENSG00000254458 (HGNC:):

ENSG00000254458 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006137997).

BP6

Variant 11-66315269-T-G is Benign according to our data. Variant chr11-66315269-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 730132.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 89 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD248	NM_020404.3 link	c.1759A>C	p.Thr587Pro	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.1759A>C	p.Thr587Pro	missense_variant	Exon 1 of 1	6	NM_020404.3	ENSP00000308117.3	Q9HCU0-1
ENSG00000254458	ENST00000534065.1 link	n.140+2277T>G		intron_variant	Intron 1 of 1	4
ENSG00000254756	ENST00000820635.1 link	n.134+3106T>G		intron_variant	Intron 1 of 3
ENSG00000254756	ENST00000820636.1 link	n.96+3106T>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000590

AC:

AN:

150786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000193

AC:

AN:

191298

AF XY:

0.000178

show subpopulations

Gnomad AFR exome

AF:

0.00193

Gnomad AMR exome

AF:

0.000278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000578

AC:

AN:

1385132

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

680714

show subpopulations

African (AFR)

AF:

0.00210

AC:

AN:

31020

American (AMR)

AF:

0.000293

AC:

AN:

34072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20752

East Asian (EAS)

AF:

0.00

AC:

AN:

39064

South Asian (SAS)

AF:

0.00

AC:

AN:

73974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5366

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074008

Other (OTH)

AF:

0.0000878

AC:

AN:

56948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000590

AC:

AN:

150906

Hom.:

Cov.:

AF XY:

0.000583

AC XY:

AN XY:

73736

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

41014

American (AMR)

AF:

0.000132

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67632

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000228

Hom.:

Bravo

AF:

0.000676

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000142

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.55

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.083

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.20

M_CAP

Benign

0.066

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.55

PhyloP100

-0.23

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.84

REVEL

Uncertain

0.30

Sift

Benign

0.11

Sift4G

Benign

0.21

Polyphen

0.0030

Vest4

0.15

MVP

0.47

MPC

0.46

ClinPred

0.0039

GERP RS

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.17

Mutation Taster

=93/7

polymorphism

(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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11-66315269-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over