20-45347641-G-C

Position:

• chr20-45347641-G-C

Variant summary

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

The NM_002999.4(SDC4):​c.60+684C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,964 control chromosomes in the GnomAD database, including 8,159 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 0.31 (8159 hom., cov: 32)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC4	NM_002999.4	c.60+684C>G		intron_variant		ENST00000372733.3	NP_002990.2
SDC4	XM_011528977.3	c.-18+684C>G		intron_variant			XP_011527279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC4	ENST00000372733.3	c.60+684C>G		intron_variant		1	NM_002999.4	ENSP00000361818	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47439 AN: 151846 Hom.: 8160 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.312 AC: 47444 AN: 151964 Hom.: 8159 Cov.: 32 AF XY: 0.316 AC XY: 23444 AN XY: 74260

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.343

Alfa AF: 0.325 Hom.: 1080

Bravo AF: 0.305

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.58

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: rs2072786; hg19: chr20-43976281;