20-45327551-T-C

Variant names:

• chr20-45327551-T-C
• rs2076025
• NM_002999.4:c.446-136A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002999.4(SDC4):​c.446-136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 997,548 control chromosomes in the GnomAD database, including 131,775 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 0.49 (18423 hom., cov: 33)
  • Exomes 𝑓: 0.52 (113352 hom.)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 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.446-136A>G		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.446-136A>G		intron	N/A	ENSP00000361818.3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74405 AN: 152048 Hom.: 18405 Cov.: 33

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.515 AC: 435554 AN: 845382 Hom.: 113352 AF XY: 0.515 AC XY: 216738 AN XY: 420706

African (AFR) AF: 0.415 AC: 8233 AN: 19846

American (AMR) AF: 0.603 AC: 12018 AN: 19928

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 8440 AN: 15980

East Asian (EAS) AF: 0.476 AC: 15490 AN: 32568

South Asian (SAS) AF: 0.508 AC: 24945 AN: 49144

European-Finnish (FIN) AF: 0.496 AC: 16953 AN: 34194

Middle Eastern (MID) AF: 0.506 AC: 1382 AN: 2732

European-Non Finnish (NFE) AF: 0.519 AC: 328217 AN: 632168

Other (OTH) AF: 0.512 AC: 19876 AN: 38822

GnomAD4 genome AF: 0.489 AC: 74465 AN: 152166 Hom.: 18423 Cov.: 33 AF XY: 0.491 AC XY: 36525 AN XY: 74388

African (AFR) AF: 0.408 AC: 16952 AN: 41550

American (AMR) AF: 0.559 AC: 8545 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1790 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2689 AN: 5180

South Asian (SAS) AF: 0.528 AC: 2548 AN: 4826

European-Finnish (FIN) AF: 0.500 AC: 5288 AN: 10580

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34960 AN: 67946

Other (OTH) AF: 0.496 AC: 1047 AN: 2112

Alfa AF: 0.438 Hom.: 2444

Bravo AF: 0.492

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.43
PhyloP100		-1.0
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: rs2076025; hg19: chr20-43956191;