20-45345097-G-T

Variant names:

• chr20-45345097-G-T
• rs2743389
• NM_002999.4:c.60+3228C>A

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+3228C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,014 control chromosomes in the GnomAD database, including 22,460 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 0.53 (22460 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 3 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]

ENSG00000275894 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 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.60+3228C>A		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.60+3228C>A		intron	N/A	ENSP00000361818.3
	SDC4	ENST00000901705.1		c.60+3228C>A		intron	N/A	ENSP00000571764.1
	SDC4	ENST00000939835.1		c.39+3249C>A		intron	N/A	ENSP00000609894.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81214 AN: 151896 Hom.: 22443 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.551

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.535 AC: 81268 AN: 152014 Hom.: 22460 Cov.: 32 AF XY: 0.541 AC XY: 40181 AN XY: 74298

African (AFR) AF: 0.447 AC: 18547 AN: 41456

American (AMR) AF: 0.657 AC: 10047 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1816 AN: 3472

East Asian (EAS) AF: 0.904 AC: 4673 AN: 5172

South Asian (SAS) AF: 0.674 AC: 3252 AN: 4826

European-Finnish (FIN) AF: 0.509 AC: 5375 AN: 10550

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.528 AC: 35849 AN: 67944

Other (OTH) AF: 0.556 AC: 1174 AN: 2110

Alfa AF: 0.513 Hom.: 7696

Bravo AF: 0.544

Asia WGS AF: 0.751 AC: 2606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.32
PhyloP100		0.45
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: rs2743389; hg19: chr20-43973737;