chr20-45343730-A-T

Variant names:

• chr20-45343730-A-T
• rs2267871
• NM_002999.4:c.60+4595T>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.60+4595T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,094 control chromosomes in the GnomAD database, including 3,768 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 0.22 (3768 hom., cov: 32)
• Consequence: SDC4 NM_002999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 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.60+4595T>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.60+4595T>A		intron	N/A	ENSP00000361818.3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33130 AN: 151976 Hom.: 3766 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.218 AC: 33131 AN: 152094 Hom.: 3768 Cov.: 32 AF XY: 0.221 AC XY: 16396 AN XY: 74336

African (AFR) AF: 0.167 AC: 6918 AN: 41518

American (AMR) AF: 0.202 AC: 3090 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2230 AN: 5162

South Asian (SAS) AF: 0.264 AC: 1270 AN: 4818

European-Finnish (FIN) AF: 0.276 AC: 2912 AN: 10566

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15160 AN: 67960

Other (OTH) AF: 0.229 AC: 482 AN: 2108

Alfa AF: 0.217 Hom.: 445

Bravo AF: 0.209

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.80
DANN	Benign	0.75
PhyloP100		-0.85
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: rs2267871; hg19: chr20-43972370;