Genetic Variant SDC1:p.Glu84Glu (chr2-20204188-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002997.5(SDC1):c.252G>A(p.Glu84Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,599,504 control chromosomes in the GnomAD database, including 50,140 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4045 hom., cov: 30)

Exomes 𝑓: 0.25 ( 46095 hom. )

Consequence

SDC1
NM_002997.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.65

Publications

15 publications found

Variant links:

Genes affected

SDC1 (HGNC:10658): (syndecan 1) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-1 expression has been detected in several different tumor types. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein. [provided by RefSeq, Jul 2008]

SDC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-4.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC1	NM_002997.5 link	c.252G>A	p.Glu84Glu	synonymous_variant	Exon 3 of 5	ENST00000254351.9	NP_002988.4	P18827

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC1	ENST00000254351.9 link	c.252G>A	p.Glu84Glu	synonymous_variant	Exon 3 of 5	1	NM_002997.5	ENSP00000254351.4		P18827

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34122

AN:

151830

Hom.:

4043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.235

GnomAD2 exomes

AF:

0.225

AC:

54061

AN:

240036

AF XY:

0.227

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.255

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.249

AC:

360569

AN:

1447556

Hom.:

46095

Cov.:

AF XY:

0.248

AC XY:

178363

AN XY:

720566

show subpopulations

African (AFR)

AF:

0.170

AC:

5706

AN:

33470

American (AMR)

AF:

0.211

AC:

9447

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

8300

AN:

26126

East Asian (EAS)

AF:

0.104

AC:

4112

AN:

39696

South Asian (SAS)

AF:

0.176

AC:

15181

AN:

86250

European-Finnish (FIN)

AF:

0.263

AC:

10361

AN:

39412

Middle Eastern (MID)

AF:

0.248

AC:

1431

AN:

5762

European-Non Finnish (NFE)

AF:

0.262

AC:

291222

AN:

1111834

Other (OTH)

AF:

0.246

AC:

14809

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

16775

33551

50326

67102

83877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9734

19468

29202

38936

48670

<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:

0.225

AC:

34126

AN:

151948

Hom.:

4045

Cov.:

AF XY:

0.225

AC XY:

16690

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.170

AC:

7044

AN:

41450

American (AMR)

AF:

0.211

AC:

3226

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1094

AN:

3466

East Asian (EAS)

AF:

0.100

AC:

517

AN:

5152

South Asian (SAS)

AF:

0.169

AC:

810

AN:

4804

European-Finnish (FIN)

AF:

0.280

AC:

2962

AN:

10582

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17804

AN:

67918

Other (OTH)

AF:

0.233

AC:

492

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1347

2694

4041

5388

6735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.217

Hom.:

1311

Bravo

AF:

0.220

Asia WGS

AF:

0.137

AC:

476

AN:

3478

EpiCase

AF:

0.258

EpiControl

AF:

0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.045

(source)

DANN

Benign

0.55

PhyloP100

-4.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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