rs7110351

Variant names:

• chr11-66315234-G-A
• rs7110351
• NM_020404.3:c.1794C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020404.3(CD248):​c.1794C>T​(p.Ser598Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,529,374 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (7 hom.)
• Consequence: CD248 NM_020404.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.823
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-66315234-G-A is Benign according to our data. Variant chr11-66315234-G-A is described in ClinVar as [Benign]. Clinvar id is 786197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.823 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000423 (582/1377214) while in subpopulation AFR AF = 0.0162 (497/30596). AF 95% confidence interval is 0.0151. There are 7 homozygotes in GnomAdExome4. There are 249 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 633 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD248	NM_020404.3	c.1794C>T	p.Ser598Ser	synonymous_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.1794C>T	p.Ser598Ser	synonymous_variant	Exon 1 of 1	6	NM_020404.3	ENSP00000308117.3
ENSG00000254458	ENST00000534065.1	n.140+2242G>A		intron_variant	Intron 1 of 1	4
ENSG00000254756	ENST00000820635.1	n.134+3071G>A		intron_variant	Intron 1 of 3
ENSG00000254756	ENST00000820636.1	n.96+3071G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00413 AC: 628 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

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: 0.0000294

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00133 AC: 243 AN: 182254 AF XY: 0.000981

Gnomad AFR exome AF: 0.0146

Gnomad AMR exome AF: 0.000666

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: 0.000478

GnomAD4 exome AF: 0.000423 AC: 582 AN: 1377214 Hom.: 7 Cov.: 31 AF XY: 0.000368 AC XY: 249 AN XY: 676416

African (AFR) AF: 0.0162 AC: 497 AN: 30596

American (AMR) AF: 0.000836 AC: 26 AN: 31084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20200

East Asian (EAS) AF: 0.00 AC: 0 AN: 39078

South Asian (SAS) AF: 0.0000833 AC: 6 AN: 71994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49714

Middle Eastern (MID) AF: 0.000375 AC: 2 AN: 5332

European-Non Finnish (NFE) AF: 0.00000280 AC: 3 AN: 1072582

Other (OTH) AF: 0.000848 AC: 48 AN: 56634

GnomAD4 genome AF: 0.00416 AC: 633 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.00407 AC XY: 303 AN XY: 74394

African (AFR) AF: 0.0147 AC: 611 AN: 41490

American (AMR) AF: 0.000719 AC: 11 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00327 Hom.: 2

Bravo AF: 0.00428

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.54
PhyloP100		0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs7110351; hg19: chr11-66082705;