Genetic Variant SDC4:c.*1497A>G (chr20-45325767-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002999.4(SDC4):c.*1497A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,054 control chromosomes in the GnomAD database, including 4,985 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 0.25 ( 4984 hom., cov: 32)

Exomes 𝑓: 0.27 ( 1 hom. )

Consequence

SDC4
NM_002999.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.60

Publications

20 publications found

Variant links:

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]

SDC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC4	NM_002999.4	MANE Select	c.*1497A>G		3_prime_UTR	Exon 5 of 5	NP_002990.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDC4	ENST00000372733.3	TSL:1 MANE Select	c.*1497A>G	3_prime_UTR	Exon 5 of 5	ENSP00000361818.3	P31431-1
SDC4	ENST00000901705.1		c.*1497A>G	3_prime_UTR	Exon 5 of 5	ENSP00000571764.1
SDC4	ENST00000939835.1		c.*1497A>G	3_prime_UTR	Exon 5 of 5	ENSP00000609894.1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38304

AN:

151884

Hom.:

4977

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.227

GnomAD4 exome

AF:

0.269

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.214

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.252

AC:

38338

AN:

152002

Hom.:

4984

Cov.:

AF XY:

0.248

AC XY:

18394

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.327

AC:

13549

AN:

41420

American (AMR)

AF:

0.211

AC:

3219

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

743

AN:

3468

East Asian (EAS)

AF:

0.422

AC:

2174

AN:

5156

South Asian (SAS)

AF:

0.172

AC:

831

AN:

4820

European-Finnish (FIN)

AF:

0.205

AC:

2170

AN:

10586

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14933

AN:

67954

Other (OTH)

AF:

0.229

AC:

485

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1479

2958

4437

5916

7395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.233

Hom.:

3380

Bravo

AF:

0.262

Asia WGS

AF:

0.303

AC:

1050

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.98

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over