chr20-45330115-G-A

Position:

• chr20-45330115-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002999.4(SDC4):​c.445+251C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,140 control chromosomes in the GnomAD database, including 44,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.76 (44170 hom., cov: 33)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.127

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-45330115-G-A is Benign according to our data. Variant chr20-45330115-G-A is described in ClinVar as [Benign]. Clinvar id is 444111.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC4	NM_002999.4	c.445+251C>T		intron_variant		ENST00000372733.3
SDC4	XM_011528977.3	c.229+251C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC4	ENST00000372733.3	c.445+251C>T		intron_variant		1	NM_002999.4	P1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115679 AN: 152022 Hom.: 44138 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.761 AC: 115764 AN: 152140 Hom.: 44170 Cov.: 33 AF XY: 0.760 AC XY: 56557 AN XY: 74384

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.757

Alfa AF: 0.756 Hom.: 10660

Bravo AF: 0.762

Asia WGS AF: 0.845 AC: 2939 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Type 2 diabetes mellitus Benign:1

Benign, no assertion criteria provided

case-control

Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institutes of Health

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.56

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: rs2425696; hg19: chr20-43958755;