rs2251252

Variant names:

• chr20-45342717-G-A
• rs2251252
• NM_002999.4:c.60+5608C>T

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+5608C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,886 control chromosomes in the GnomAD database, including 14,400 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 0.43 (14400 hom., cov: 31)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC4	NM_002999.4	c.60+5608C>T		intron_variant	Intron 1 of 4	ENST00000372733.3	NP_002990.2
SDC4	XM_011528977.3	c.-18+5608C>T		intron_variant	Intron 1 of 3		XP_011527279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC4	ENST00000372733.3	c.60+5608C>T		intron_variant	Intron 1 of 4	1	NM_002999.4	ENSP00000361818.3

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65894 AN: 151768 Hom.: 14395 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.434 AC: 65926 AN: 151886 Hom.: 14400 Cov.: 31 AF XY: 0.430 AC XY: 31911 AN XY: 74226

African (AFR) AF: 0.445 AC: 18408 AN: 41372

American (AMR) AF: 0.406 AC: 6198 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3464

East Asian (EAS) AF: 0.474 AC: 2451 AN: 5172

South Asian (SAS) AF: 0.373 AC: 1794 AN: 4812

European-Finnish (FIN) AF: 0.388 AC: 4092 AN: 10556

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.441 AC: 29973 AN: 67942

Other (OTH) AF: 0.445 AC: 939 AN: 2108

Alfa AF: 0.436 Hom.: 7715

Bravo AF: 0.436

Asia WGS AF: 0.438 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.26
PhyloP100		-0.027
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: rs2251252; hg19: chr20-43971357;