rs11544860

Positions:

• chr2-20224894-G-A
• chr2-20224894-G-C

Variant summary

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

The NM_002997.5(SDC1):​c.-27C>T variant causes a 5 prime UTR 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC1	NM_002997.5	c.-27C>T		5_prime_UTR_variant	1/5	ENST00000254351.9
SDC1	NM_001006946.2	c.-27C>T		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC1	ENST00000254351.9	c.-27C>T		5_prime_UTR_variant	1/5	1	NM_002997.5	P1
SDC1	ENST00000403076.5	c.-27C>T		5_prime_UTR_variant	1/4	1
SDC1	ENST00000381150.5	c.-27C>T		5_prime_UTR_variant	2/6	5		P1
SDC1	ENST00000447124.1	c.-27C>T		5_prime_UTR_variant, NMD_transcript_variant	1/4	4

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6655 AN: 151878 Hom.: 204 Cov.: 33

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

GnomAD3 exomes AF: 0.0633 AC: 21 AN: 332 Hom.: 0 AF XY: 0.0798 AC XY: 15 AN XY: 188

Gnomad AMR exome AF: 0.00

Gnomad SAS 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.: 31 AF XY: 0.0652 AC XY: 32722 AN XY: 501660

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.0433

Gnomad4 ASJ exome AF: 0.0583

Gnomad4 EAS exome AF: 0.0000827

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0496

Gnomad4 NFE exome AF: 0.0703

Gnomad4 OTH exome AF: 0.0597

GnomAD4 genome AF: 0.0438 AC: 6656 AN: 151986 Hom.: 204 Cov.: 33 AF XY: 0.0421 AC XY: 3129 AN XY: 74286

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0443

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.0452

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0155 Hom.: 3

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	13
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs11544860; hg19: chr2-20424655;