rs2251252

chr20-45342717-G-A

Variant summary

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

The NM_002999.4(SDC4):c.60+5608C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,886 control chromosomes in the GnomAD database, including 14,400 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 0.43 (14400 hom., cov: 31)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC4	NM_002999.4	c.60+5608C>T		intron_variant		ENST00000372733.3
SDC4	XM_011528977.3	c.-18+5608C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC4	ENST00000372733.3	c.60+5608C>T		intron_variant		1	NM_002999.4	P1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65894 AN: 151768 Hom.: 14395 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.446

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.434 AC: 65926 AN: 151886 Hom.: 14400 Cov.: 31 AF XY: 0.430 AC XY: 31911 AN XY: 74226

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.445

Alfa AF: 0.437 Hom.: 4792

Bravo AF: 0.436

Asia WGS AF: 0.438 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.8
Dann	Benign	0.26

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: rs2251252; hg19: chr20-43971357;