chr17-50165951-C-A

Variant names:

• chr17-50165951-C-A
• rs75145501
• ENST00000895791.1:c.-11-79C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000895791.1(SGCA):​c.-11-79C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00929 in 1,045,858 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0072 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (45 hom.)
• Consequence: SGCA ENST00000895791.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.31
• Publications: 1 publications found

Genes affected

SGCA (HGNC:10805): (sarcoglycan alpha) This gene encodes a component of the dystrophin-glycoprotein complex (DGC), which is critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. Its expression is thought to be restricted to striated muscle. Mutations in this gene result in type 2D autosomal recessive limb-girdle muscular dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

SGCA Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia
• autosomal recessive limb-girdle muscular dystrophy type 2D

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000253730 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-50165951-C-A is Benign according to our data. Variant chr17-50165951-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1179547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00718 (1093/152246) while in subpopulation NFE AF = 0.0113 (769/68006). AF 95% confidence interval is 0.0106. There are 9 homozygotes in GnomAd4. There are 533 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000895791.1. 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
	SGCA	NM_000023.4	MANE Select	c.-90C>A		upstream_gene	N/A	NP_000014.1	A0A0S2Z4Q1
	SGCA	NM_001135697.3		c.-90C>A		upstream_gene	N/A	NP_001129169.1	A0A0S2Z4P8
	SGCA	NR_135553.2		n.-54C>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCA	ENST00000895791.1		c.-11-79C>A		intron	N/A	ENSP00000565850.1
	SGCA	ENST00000895792.1		c.-11-79C>A		intron	N/A	ENSP00000565851.1
	SGCA	ENST00000513942.5	TSL:3	n.103+1635C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00718 AC: 1093 AN: 152128 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00965 AC: 8624 AN: 893612 Hom.: 45 Cov.: 12 AF XY: 0.00939 AC XY: 4387 AN XY: 467066

African (AFR) AF: 0.00159 AC: 36 AN: 22620

American (AMR) AF: 0.00456 AC: 196 AN: 42994

Ashkenazi Jewish (ASJ) AF: 0.00452 AC: 98 AN: 21696

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37110

South Asian (SAS) AF: 0.00219 AC: 161 AN: 73356

European-Finnish (FIN) AF: 0.00999 AC: 525 AN: 52550

Middle Eastern (MID) AF: 0.00188 AC: 6 AN: 3192

European-Non Finnish (NFE) AF: 0.0121 AC: 7234 AN: 598768

Other (OTH) AF: 0.00888 AC: 367 AN: 41326

GnomAD4 genome AF: 0.00718 AC: 1093 AN: 152246 Hom.: 9 Cov.: 32 AF XY: 0.00716 AC XY: 533 AN XY: 74422

African (AFR) AF: 0.00193 AC: 80 AN: 41540

American (AMR) AF: 0.00536 AC: 82 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4828

European-Finnish (FIN) AF: 0.0117 AC: 124 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0113 AC: 769 AN: 68006

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00974 Hom.: 0

Bravo AF: 0.00661

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.4
DANN	Benign	0.75
PhyloP100		2.3
PromoterAI		0.17	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs75145501; hg19: chr17-48243312; COSMIC: COSV56251727;