rs3741367

Variant names:

• chr11-66315658-T-C
• rs3741367
• NM_020404.3:c.1370A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.38 (11818 hom., cov: 31)
  • Exomes 𝑓: 0.43 (142065 hom.)
• Consequence: CD248 NM_020404.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

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]

ENSG00000254458 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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	c.1370A>G	p.His457Arg	missense_variant	Exon 1 of 1	ENST00000311330.4	NP_065137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD248	ENST00000311330.4	c.1370A>G	p.His457Arg	missense_variant	Exon 1 of 1	6	NM_020404.3	ENSP00000308117.3
ENSG00000254458	ENST00000534065.1	n.140+2666T>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57073 AN: 151514 Hom.: 11816 Cov.: 31

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

GnomAD3 exomes AF: 0.409 AC: 102635 AN: 250962 Hom.: 23093 AF XY: 0.402 AC XY: 54467 AN XY: 135644

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 SAS exome AF: 0.239

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

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.377 AC: 57093 AN: 151632 Hom.: 11818 Cov.: 31 AF XY: 0.376 AC XY: 27847 AN XY: 74040

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.357

Alfa AF: 0.429 Hom.: 34397

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
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

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

Other links and lift over

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