rs780843035

Variant names:

• chr11-66315067-T-C
• rs780843035
• NM_020404.3:c.1961A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-66315067-T-C
• chr11-66315067-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020404.3(CD248):​c.1961A>G​(p.Lys654Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 1,572,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. K654T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD248 NM_020404.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053901672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD248	NM_020404.3	c.1961A>G	p.Lys654Arg	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.1961A>G	p.Lys654Arg	missense_variant	Exon 1 of 1	6	NM_020404.3	ENSP00000308117.3
ENSG00000254458	ENST00000534065.1	n.140+2075T>C		intron_variant	Intron 1 of 1	4
ENSG00000254756	ENST00000820635.1	n.134+2904T>C		intron_variant	Intron 1 of 3
ENSG00000254756	ENST00000820636.1	n.96+2904T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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: 0.00000464 AC: 1 AN: 215682 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1420810 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 701630

African (AFR) AF: 0.00 AC: 0 AN: 32734

American (AMR) AF: 0.00 AC: 0 AN: 41582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22934

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39362

South Asian (SAS) AF: 0.00 AC: 0 AN: 78976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5556

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090428

Other (OTH) AF: 0.00 AC: 0 AN: 58638

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74280

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.63
DANN	Benign	0.95
DEOGEN2	Benign	0.081	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.59
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.17
Sift	Benign	0.20	T
Sift4G	Benign	0.49	T
Polyphen		0.0010	B
Vest4		0.091
MutPred		0.16		Loss of ubiquitination at K654 (P = 0.0051);
MVP		0.39
MPC		0.29
ClinPred		0.039	T
GERP RS		1.1
Varity_R		0.032
gMVP		0.11
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs780843035; hg19: chr11-66082538;