rs2072786

Variant names:

• chr20-45347641-G-C
• rs2072786
• NM_002999.4:c.60+684C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SDC4	NM_002999.4	c.60+684C>G		intron_variant	Intron 1 of 4	ENST00000372733.3	NP_002990.2
SDC4	XM_011528977.3	c.-18+684C>G		intron_variant	Intron 1 of 3		XP_011527279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC4	ENST00000372733.3	c.60+684C>G		intron_variant	Intron 1 of 4	1	NM_002999.4	ENSP00000361818.3

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

African (AFR) AF: 0.167 AC: 6939 AN: 41472

American (AMR) AF: 0.364 AC: 5559 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1358 AN: 3466

East Asian (EAS) AF: 0.425 AC: 2189 AN: 5152

South Asian (SAS) AF: 0.356 AC: 1711 AN: 4808

European-Finnish (FIN) AF: 0.391 AC: 4121 AN: 10532

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24523 AN: 67944

Other (OTH) AF: 0.343 AC: 723 AN: 2106

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
PhyloP100		0.079
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2072786; hg19: chr20-43976281;