rs4599

chr20-45325767-T-C

Variant summary

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

The NM_002999.4(SDC4):c.*1497A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,054 control chromosomes in the GnomAD database, including 4,985 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 0.25 (4984 hom., cov: 32)
  • Exomes 𝑓: 0.27 (1 hom.)
• Consequence: SDC4 NM_002999.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.60

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC4	NM_002999.4	c.*1497A>G		3_prime_UTR_variant	5/5	ENST00000372733.3
SDC4	XM_011528977.3	c.*1497A>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC4	ENST00000372733.3	c.*1497A>G		3_prime_UTR_variant	5/5	1	NM_002999.4	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38304 AN: 151884 Hom.: 4977 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.269 AC: 14 AN: 52 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 10 AN XY: 30

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.252 AC: 38338 AN: 152002 Hom.: 4984 Cov.: 32 AF XY: 0.248 AC XY: 18394 AN XY: 74306

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.229

Alfa AF: 0.236 Hom.: 1999

Bravo AF: 0.262

Asia WGS AF: 0.303 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.010
Dann	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98

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: rs4599; hg19: chr20-43954407;