8-14618928-C-G

Variant names:

• chr8-14618928-C-G
• rs2202987
• NM_139167.4:c.40-64002G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139167.4(SGCZ):​c.40-64002G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 152,258 control chromosomes in the GnomAD database, including 69,396 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 0.95 (69396 hom., cov: 33)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 1 publications found

Genes affected

SGCZ (HGNC:14075): (sarcoglycan zeta) The zeta-sarcoglycan gene measures over 465 kb and localizes to 8p22. This protein is part of the sarcoglycan complex, a group of 6 proteins. The sarcoglycans are all N-glycosylated transmembrane proteins with a short intra-cellular domain, a single transmembrane region and a large extra-cellular domain containing a carboxyl-terminal cluster with several conserved cysteine residues. The sarcoglycan complex is part of the dystrophin-associated glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extra-cellular matrix. [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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.40-64002G>C		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.40-64002G>C		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.40-64002G>C		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-89-64002G>C		intron_variant	Intron 1 of 6		NP_001309810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6	c.40-64002G>C		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145163 AN: 152140 Hom.: 69341 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.957

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.951

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

GnomAD4 genome AF: 0.954 AC: 145275 AN: 152258 Hom.: 69396 Cov.: 33 AF XY: 0.955 AC XY: 71093 AN XY: 74438

African (AFR) AF: 0.914 AC: 37992 AN: 41544

American (AMR) AF: 0.957 AC: 14633 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3412 AN: 3472

East Asian (EAS) AF: 0.922 AC: 4758 AN: 5160

South Asian (SAS) AF: 0.990 AC: 4782 AN: 4828

European-Finnish (FIN) AF: 0.979 AC: 10404 AN: 10622

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66093 AN: 68022

Other (OTH) AF: 0.951 AC: 2012 AN: 2116

Alfa AF: 0.964 Hom.: 8784

Bravo AF: 0.952

Asia WGS AF: 0.937 AC: 3261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.45
PhyloP100		-0.51
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: rs2202987; hg19: chr8-14476437;