Genetic Variant ENST00000517913.5:c.-208+603A>T (chr5-156118554-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000517913.5(SGCD):c.-208+603A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,980 control chromosomes in the GnomAD database, including 15,715 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 0.44 ( 15715 hom., cov: 32)

Consequence

SGCD
ENST00000517913.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.235

Publications

3 publications found

Variant links:

Genes affected

SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]

SGCD Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2F
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
dilated cardiomyopathy 1L
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

SGCD 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
SGCD	XM_017009724.2 link	c.-207-5302A>T	intron_variant	Intron 1 of 9	XP_016865213.1	Q92629-2
SGCD	XM_047417518.1 link	c.-207-5302A>T	intron_variant	Intron 3 of 11	XP_047273474.1
SGCD	XM_047417519.1 link	c.-207-5302A>T	intron_variant	Intron 2 of 10	XP_047273475.1
SGCD	XM_047417520.1 link	c.-164-5302A>T	intron_variant	Intron 1 of 8	XP_047273476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000517913.5 link	c.-208+603A>T		intron_variant	Intron 2 of 9	5		ENSP00000429378.1		Q92629-3

Frequencies

GnomAD3 genomes

AF:

0.444

AC:

67368

AN:

151860

Hom.:

15677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.576

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.436

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

GnomAD4 genome

AF:

0.444

AC:

67464

AN:

151980

Hom.:

15715

Cov.:

AF XY:

0.437

AC XY:

32412

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.576

AC:

23875

AN:

41446

American (AMR)

AF:

0.420

AC:

6409

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1576

AN:

3466

East Asian (EAS)

AF:

0.189

AC:

975

AN:

5160

South Asian (SAS)

AF:

0.311

AC:

1501

AN:

4820

European-Finnish (FIN)

AF:

0.387

AC:

4086

AN:

10562

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27713

AN:

67950

Other (OTH)

AF:

0.433

AC:

915

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1868

3735

5603

7470

9338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<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:

0.437

Hom.:

1863

Bravo

AF:

0.449

Asia WGS

AF:

0.319

AC:

1109

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.2

(source)

DANN

Benign

0.42

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over