rs11544860

Variant names:

• chr2-20224894-G-A
• rs11544860
• NM_002997.5:c.-27C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• Publications: 3 publications found

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

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

Ensembl

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

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

GnomAD2 exomes AF: 0.0633 AC: 21 AN: 332 AF XY: 0.0798

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

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: 2 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

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

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: 1 AN: 5142

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4832

European-Finnish (FIN) AF: 0.0452 AC: 477 AN: 10550

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0668 AC: 4535 AN: 67886

Other (OTH) AF: 0.0493 AC: 104 AN: 2108

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
PhyloP100		-0.65
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=298/2	polymorphism (auto)

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: rs11544860; hg19: chr2-20424655;