20-45328870-G-A

Variant names:

• chr20-45328870-G-A
• rs985586
• NM_002999.4:c.446-1455C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002999.4(SDC4):​c.446-1455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,988 control chromosomes in the GnomAD database, including 5,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.26 (5186 hom., cov: 32)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.623
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-45328870-G-A is Benign according to our data. Variant chr20-45328870-G-A is described in ClinVar as Benign. ClinVar VariationId is 444106.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002999.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC4	NM_002999.4	MANE Select	c.446-1455C>T		intron	N/A	NP_002990.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC4	ENST00000372733.3	TSL:1 MANE Select	c.446-1455C>T		intron	N/A	ENSP00000361818.3	P31431-1
	SDC4	ENST00000901705.1		c.455-1455C>T		intron	N/A	ENSP00000571764.1
	SDC4	ENST00000939835.1		c.425-1455C>T		intron	N/A	ENSP00000609894.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38982 AN: 151868 Hom.: 5184 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.257 AC: 39006 AN: 151988 Hom.: 5186 Cov.: 32 AF XY: 0.254 AC XY: 18868 AN XY: 74292

African (AFR) AF: 0.325 AC: 13447 AN: 41436

American (AMR) AF: 0.174 AC: 2651 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2095 AN: 5170

South Asian (SAS) AF: 0.225 AC: 1082 AN: 4810

European-Finnish (FIN) AF: 0.259 AC: 2732 AN: 10568

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15605 AN: 67954

Other (OTH) AF: 0.247 AC: 522 AN: 2110

Alfa AF: 0.223 Hom.: 1722

Bravo AF: 0.255

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Type 2 diabetes mellitus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.61
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs985586; hg19: chr20-43957510;