20-45327551-T-C

Position:

• chr20-45327551-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.446-136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 997,548 control chromosomes in the GnomAD database, including 131,775 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 0.49 (18423 hom., cov: 33)
  • Exomes 𝑓: 0.52 (113352 hom.)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC4	NM_002999.4	c.446-136A>G		intron_variant		ENST00000372733.3	NP_002990.2
SDC4	XM_011528977.3	c.230-136A>G		intron_variant			XP_011527279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC4	ENST00000372733.3	c.446-136A>G		intron_variant		1	NM_002999.4	ENSP00000361818.3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74405 AN: 152048 Hom.: 18405 Cov.: 33

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.515 AC: 435554 AN: 845382 Hom.: 113352 AF XY: 0.515 AC XY: 216738 AN XY: 420706

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.512

GnomAD4 genome AF: 0.489 AC: 74465 AN: 152166 Hom.: 18423 Cov.: 33 AF XY: 0.491 AC XY: 36525 AN XY: 74388

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.496

Alfa AF: 0.438 Hom.: 2444

Bravo AF: 0.492

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2076025; hg19: chr20-43956191;