Genetic Variant NM_002999.4:c.61-965T>C (chr20-45336885-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.407

Publications

0 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 gene

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.61-965T>C		intron	N/A	NP_002990.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SDC4	ENST00000372733.3	TSL:1 MANE Select	c.61-965T>C	intron	N/A	ENSP00000361818.3	P31431-1
SDC4	ENST00000901705.1		c.61-965T>C	intron	N/A	ENSP00000571764.1
SDC4	ENST00000939835.1		c.40-965T>C	intron	N/A	ENSP00000609894.1

Frequencies

GnomAD3 genomes

AF:

0.00400

AC:

607

AN:

151918

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00421

AC XY:

313

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41470

American (AMR)

AF:

0.0288

AC:

440

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.0246

AC:

127

AN:

5164

South Asian (SAS)

AF:

0.00167

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

67948

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00430

Hom.:

Bravo

AF:

0.00899

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Type 2 diabetes mellitus (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.4

(source)

DANN

Benign

0.75

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism

(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

Publications

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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