20-45335648-T-C

Position:

• chr20-45335648-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000372733.3(SDC4):​c.199+134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 890,750 control chromosomes in the GnomAD database, including 116,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.49 (18639 hom., cov: 30)
  • Exomes 𝑓: 0.51 (97588 hom.)
• Consequence: SDC4 ENST00000372733.3 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0170

Genes affected

SDC4 (HGNC:10661): (syndecan 4) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan that functions as a receptor in intracellular signaling. The encoded protein is found as a homodimer and is a member of the syndecan proteoglycan family. This gene is found on chromosome 20, while a pseudogene has been found on chromosome 22. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-45335648-T-C is Benign according to our data. Variant chr20-45335648-T-C is described in ClinVar as [Benign]. Clinvar id is 444113.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC4	NM_002999.4	c.199+134A>G		intron_variant		ENST00000372733.3	NP_002990.2
SDC4	XM_011528977.3	c.-17-2579A>G		intron_variant			XP_011527279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC4	ENST00000372733.3	c.199+134A>G		intron_variant		1	NM_002999.4	ENSP00000361818	P1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74536 AN: 151748 Hom.: 18624 Cov.: 30

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.510 AC: 376881 AN: 738884 Hom.: 97588 AF XY: 0.510 AC XY: 193171 AN XY: 378628

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.628

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.506

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.491 AC: 74588 AN: 151866 Hom.: 18639 Cov.: 30 AF XY: 0.494 AC XY: 36663 AN XY: 74210

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.504

Alfa AF: 0.495 Hom.: 2246

Bravo AF: 0.492

Asia WGS AF: 0.504 AC: 1756 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Type 2 diabetes mellitus Benign:1

Benign, no assertion criteria provided

case-control

Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institutes of Health

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.69

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: rs2072792; hg19: chr20-43964288;