rs4265186

Variant names:

• chr8-14926227-G-A
• rs4265186
• NM_139167.4:c.39+311358C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-14926227-G-A
• chr8-14926227-G-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.39+311358C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,928 control chromosomes in the GnomAD database, including 27,065 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 0.57 (27065 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.39+311358C>T		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.39+311358C>T		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.39+311358C>T		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-90+311358C>T		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.39+311358C>T		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87060 AN: 151808 Hom.: 27007 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.574 AC: 87175 AN: 151928 Hom.: 27065 Cov.: 32 AF XY: 0.568 AC XY: 42142 AN XY: 74222

African (AFR) AF: 0.826 AC: 34256 AN: 41488

American (AMR) AF: 0.468 AC: 7143 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1394 AN: 5160

South Asian (SAS) AF: 0.517 AC: 2488 AN: 4814

European-Finnish (FIN) AF: 0.485 AC: 5082 AN: 10486

Middle Eastern (MID) AF: 0.486 AC: 140 AN: 288

European-Non Finnish (NFE) AF: 0.497 AC: 33767 AN: 67930

Other (OTH) AF: 0.523 AC: 1103 AN: 2110

Alfa AF: 0.497 Hom.: 14082

Bravo AF: 0.581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.56
PhyloP100		-0.34
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: rs4265186; hg19: chr8-14783736;