rs11476

Variant names:

• chr3-8746512-A-T
• rs11476
• NM_033337.3:c.*645A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001234.5(CAV3):​c.*549A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,820 control chromosomes in the GnomAD database, including 13,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13442 hom., cov: 30)
  • Exomes 𝑓: 0.36 (5 hom.)
• Consequence: CAV3 NM_001234.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: -0.110
• Publications: 9 publications found

Genes affected

CAV3 (HGNC:1529): (caveolin 3) This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008]

OXTR (HGNC:8529): (oxytocin receptor) The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. The oxytocin-oxytocin receptor system plays an important role in the uterus during parturition. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-8746512-A-T is Benign according to our data. Variant chr3-8746512-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 31706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001234.5. 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
	CAV3	NM_033337.3	MANE Select	c.*645A>T		3_prime_UTR	Exon 2 of 2	NP_203123.1
	CAV3	NM_001234.5		c.*549A>T		3_prime_UTR	Exon 3 of 3	NP_001225.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV3	ENST00000343849.3	TSL:1 MANE Select	c.*645A>T		3_prime_UTR	Exon 2 of 2	ENSP00000341940.2
	CAV3	ENST00000397368.2	TSL:1	c.*549A>T		3_prime_UTR	Exon 3 of 3	ENSP00000380525.2
	CAV3	ENST00000472766.1	TSL:2	n.155+12522A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63064 AN: 151636 Hom.: 13436 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.364 AC: 24 AN: 66 Hom.: 5 Cov.: 0 AF XY: 0.325 AC XY: 13 AN XY: 40

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.333 AC: 2 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.391 AC: 18 AN: 46

Other (OTH) AF: 0.250 AC: 2 AN: 8

GnomAD4 genome AF: 0.416 AC: 63115 AN: 151754 Hom.: 13442 Cov.: 30 AF XY: 0.416 AC XY: 30844 AN XY: 74124

African (AFR) AF: 0.385 AC: 15929 AN: 41342

American (AMR) AF: 0.442 AC: 6750 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1460 AN: 3460

East Asian (EAS) AF: 0.312 AC: 1605 AN: 5138

South Asian (SAS) AF: 0.223 AC: 1072 AN: 4812

European-Finnish (FIN) AF: 0.546 AC: 5746 AN: 10520

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.432 AC: 29328 AN: 67914

Other (OTH) AF: 0.398 AC: 840 AN: 2112

Alfa AF: 0.435 Hom.: 1949

Bravo AF: 0.412

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (3)
-	-	1	Caveolinopathy (1)
-	-	1	Congenital long QT syndrome (1)
-	-	1	Limb-Girdle Muscular Dystrophy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		-0.11
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: rs11476; hg19: chr3-8788198;