20-45341200-C-T

Variant names:

• chr20-45341200-C-T
• rs2267868
• NM_002999.4:c.61-5280G>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.61-5280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,200 control chromosomes in the GnomAD database, including 49,536 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 0.80 (49536 hom., cov: 33)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC4	NM_002999.4	MANE Select	c.61-5280G>A		intron	N/A	NP_002990.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC4	ENST00000372733.3	TSL:1 MANE Select	c.61-5280G>A		intron	N/A	ENSP00000361818.3

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122208 AN: 152082 Hom.: 49484 Cov.: 33

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.804 AC: 122315 AN: 152200 Hom.: 49536 Cov.: 33 AF XY: 0.803 AC XY: 59722 AN XY: 74396

African (AFR) AF: 0.901 AC: 37423 AN: 41532

American (AMR) AF: 0.766 AC: 11720 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2497 AN: 3472

East Asian (EAS) AF: 0.945 AC: 4898 AN: 5182

South Asian (SAS) AF: 0.757 AC: 3651 AN: 4820

European-Finnish (FIN) AF: 0.775 AC: 8201 AN: 10584

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51382 AN: 67994

Other (OTH) AF: 0.784 AC: 1654 AN: 2110

Alfa AF: 0.766 Hom.: 26545

Bravo AF: 0.811

Asia WGS AF: 0.859 AC: 2989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.64
PhyloP100		0.13
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: rs2267868; hg19: chr20-43969840;