20-45336885-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_002999.4(SDC4):c.61-965T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 152,036 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.0040 (16 hom., cov: 31)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.407

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=-0.82).
• BP6: Variant 20-45336885-A-G is Benign according to our data. Variant chr20-45336885-A-G is described in ClinVar as [Benign]. Clinvar id is 444109.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00402 (611/152036) while in subpopulation AMR AF= 0.0288 (440/15268). AF 95% confidence interval is 0.0266. There are 16 homozygotes in gnomad4. There are 313 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC4	NM_002999.4	c.61-965T>C		intron_variant		ENST00000372733.3
SDC4	XM_011528977.3	c.-17-3816T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC4	ENST00000372733.3	c.61-965T>C		intron_variant		1	NM_002999.4	P1

Frequencies

GnomAD3 genomes AF: 0.00400 AC: 607 AN: 151918 Hom.: 15 Cov.: 31

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00192

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

GnomAD4 genome AF: 0.00402 AC: 611 AN: 152036 Hom.: 16 Cov.: 31 AF XY: 0.00421 AC XY: 313 AN XY: 74334

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.0288

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0246

Gnomad4 SAS AF: 0.00167

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00430 Hom.: 2

Bravo AF: 0.00899

Asia WGS AF: 0.0100 AC: 35 AN: 3478

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	-0.82
Cadd	Benign	4.4
Dann	Benign	0.75

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: rs147593522; hg19: chr20-43965525;