Genetic Variant NM_002997.5:c.-27C>T (chr2-20224894-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002997.5(SDC1):c.-27C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 1,212,194 control chromosomes in the GnomAD database, including 2,595 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 0.044 ( 204 hom., cov: 33)

Exomes 𝑓: 0.065 ( 2391 hom. )

Consequence

SDC1
NM_002997.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.648

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SDC1	NM_002997.5 link	c.-27C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	ENST00000254351.9	NP_002988.4	P18827
SDC1	NM_002997.5 link	c.-27C>T	5_prime_UTR_variant	Exon 1 of 5	ENST00000254351.9	NP_002988.4	P18827
SDC1	NM_001006946.2 link	c.-27C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 6		NP_001006947.2	P18827
SDC1	NM_001006946.2 link	c.-27C>T	5_prime_UTR_variant	Exon 2 of 6		NP_001006947.2	P18827

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC1	ENST00000254351.9 link	c.-27C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	1	NM_002997.5	ENSP00000254351.4		P18827
SDC1	ENST00000254351.9 link	c.-27C>T		5_prime_UTR_variant	Exon 1 of 5	1	NM_002997.5	ENSP00000254351.4		P18827

Frequencies

GnomAD3 genomes

AF:

0.0438

AC:

6655

AN:

151878

Hom.:

204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0444

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0452

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0668

Gnomad OTH

AF:

0.0494

GnomAD2 exomes

AF:

0.0633

AC:

AN:

332

AF XY:

0.0798

show subpopulations

Gnomad AMR exome

AF:

0.00

Gnomad NFE exome

AF:

0.0660

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0652

AC:

69122

AN:

1060208

Hom.:

2391

Cov.:

AF XY:

0.0652

AC XY:

32722

AN XY:

501660

show subpopulations

African (AFR)

AF:

0.0113

AC:

247

AN:

21918

American (AMR)

AF:

0.0433

AC:

327

AN:

7556

Ashkenazi Jewish (ASJ)

AF:

0.0583

AC:

764

AN:

13114

East Asian (EAS)

AF:

0.0000827

AC:

AN:

24192

South Asian (SAS)

AF:

0.0120

AC:

238

AN:

19758

European-Finnish (FIN)

AF:

0.0496

AC:

1027

AN:

20696

Middle Eastern (MID)

AF:

0.0479

AC:

133

AN:

2778

European-Non Finnish (NFE)

AF:

0.0703

AC:

63886

AN:

908354

Other (OTH)

AF:

0.0597

AC:

2498

AN:

41842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

3430

6861

10291

13722

17152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2734

5468

8202

10936

13670

<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:

0.0438

AC:

6656

AN:

151986

Hom.:

204

Cov.:

AF XY:

0.0421

AC XY:

3129

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0127

AC:

529

AN:

41518

American (AMR)

AF:

0.0443

AC:

677

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0594

AC:

206

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5142

South Asian (SAS)

AF:

0.0124

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0452

AC:

477

AN:

10550

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0668

AC:

4535

AN:

67886

Other (OTH)

AF:

0.0493

AC:

104

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

336

672

1009

1345

1681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0155

Hom.:

Bravo

AF:

0.0442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

-0.65

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=298/2

polymorphism (auto)

(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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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